Metabolic and psychological effects of short-term increased consumption of less-processed foods in daily diets: A Pilot Study.

AIM: This study evaluated whether the consumption of locally produced food without additives might have a positive effect on known risk factors for non-communicable diseases (NCDs) such as hypertension, and levels of fasting glucose and visceral adipose tissue (VAT). Attention was focused on various types of cheese, sausages, fresh pasta, pastries, biscuits and chocolate without additives to make them palatable and durable for transport. METHODS: Healthy volunteers were randomized to purchase the foods under study from either local producers not using additives (group 1) or supermarkets (group 2). At baseline and after 6 months, both groups underwent evaluation for weight, blood pressure, VAT, serum sodium, potassium, fasting glucose, insulin, C-peptide and creatinine levels, and also the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI-II) by examiners blinded to group allocation. At baseline, the state part of the STAI and Wechsler Adult Intelligence Scale IV were also performed, and body mass index, HOMA index and estimated glomerular filtration rate calculated. RESULTS: Data for 159 subjects (89 in group 1, 70 in group 2) were analyzed. Baseline evaluations did not differ between groups. At 6 months, HOMA scores and fasting glucose levels were lower in group 1 than in group 2 (P<0.01). Also, in group 1, VAT (P=0.006), systolic blood pressure (P=0.001) and BDI-II score (P=0.0005) were decreased, whereas serum fasting glucose (P=0.04) and C-peptide (P=0.03) levels, and diastolic blood pressure (P=0.02), were increased in group 2. CONCLUSION: Consumption of the locally produced food under study improved some of the major risk factors for NCDs after 6 months.

Altered resting state attentional networks in diabetic neuropathic pain.

BACKGROUND: Chronic pain can be considered as a highly salient stimulus that continuously taxes the attentional and salience processing networks, thus interfering with cognitive abilities and, more specifically, consuming attentional resources. The aim of the paper was to explore whether and how diabetic neuropathic pain (NP) affects attentional networks. METHODS: The authors sought to achieve this by investigating resting state functional connectivity (rsFC) in diabetic NP patients and comparing it with that of matched healthy controls. RESULTS: NP patients showed a widespread reduction in connectivity in both the dorsal and ventral attentional networks, as well as in the dorsal anterior cingulated cortex (ACC), typically implicated in salience processing. The authors also found a generalised reduction in the length of functional connections in the NP group: in all the examined networks, the Euclidean distance between connected voxels was significantly shorter in patients than in controls. CONCLUSION: In diabetic NP, a parieto-fronto-cingulate network controlling attention to external stimuli is impaired. In line with previous studies, chronic pain can disrupt the synchrony of a common pool of brain areas, involved in self-monitoring, pain processing and salience detection.

Differential diagnosis of chronic dysimmune demyelinating polyneuropathies with and without anti-MAG antibodies.

The distinction between chronic demyelinating polyneuropathies associated with IgM paraproteinemia and anti-myelin-associated glycoprotein (MAG) antibodies (MAG-PN) and chronic inflammatory demyelinating polyneuropathies (CIDPs) relies on the anti-MAG antibodies assay. The aim of the study was to identify clinical and electrophysiological features suggesting a diagnosis of MAG-PN. Fourteen patients with MAG-PN and 35 with CIDP were included, and a discriminant analysis was performed to identify the clinical and electrophysiological features suggestive of MAG-PN. Pure sensory clinical phenotype, low median and ulnar terminal latency index, and absence of M responses in the lower limbs were significantly associated with the diagnosis of MAG-PN, and indicate a moderate to large increase in probability of this diagnosis in patients with chronic dysimmune demyelinating polyneuropathies.

Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study.

The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalidomide sensory neurotoxicity was found to be cumulative dose dependent but occurs only when the total dose is relatively high (>20 g). The risk of developing sensory neuropathy is around 10% below this threshold but increases with higher doses.

Thalidomide neuropathy: clinical, electrophysiological and neuroradiological features.

OBJECTIVE: Thalidomide is a promising therapy for multiple myeloma. Sensory neuropathy is a side effect of thalidomide and resulted to be partially reversible in 50% of cases, suggesting a sensory ganglionopathy. Spinal cord magnetic resonance imaging (MRI) was found to be useful in the diagnosis of sensory ganglionopathies and we use it to determine if thalidomide neuropathy has features of a ganglionopathy. MATERIAL AND METHODS: Six patients with multiple myeloma developed thalidomide-induced polyneuropathy. Nerve conduction studies, somatosensory-evoked potentials (SEPs) and cervical and dorsal spinal cord MRI were obtained in all. RESULTS: All patients had a sensory neuropathy, with clinical or electrophysiological abnormalities involving all four limbs. Spinal cord MRI showed high signal intensity in the posterior columns in only one patient, with abnormal central conduction time at SEPs. CONCLUSION: Our results suggest that thalidomide can induce either an axonal length-dependent neuropathy or, less frequently, a ganglionopathy.

Different clinical, electrophysiological and immunological features of CIDP associated with paraproteinaemia.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is frequently associated with monoclonal gammopathies of undetermined significance (MGUS), Waldenström disease and osteosclerotic myeloma. There are still controversies about the role of these paraproteinaemias in determining the clinical features and the response to treatment of CIDP. We review the clinical, electrophysiological and immunological features and the response to treatment of patients with CIDP associated with paraproteinaemias. The available literature suggest some conclusions: presence of antimyelin-associated glycoprotein (MAG) antibody (Ab) identifies patients with mainly sensory CIDP and low response to treatment; CIDP associated with IgM-paraproteinaemia without anti-MAG Ab probably are similar to CIDP not associated with paraproteinaemia as well as CIDP with IgG- or IgA-MGUS; however, some patients with IgA-MGUS can show features similar to CIDP with IgM paraproteinaemia and anti-MAG Ab. Low response to immunomodulating treatment in patients with mainly motor CIDP should prompt a careful research of an underlying osteosclerotic myeloma.

Intracranial stimulation of the facial nerve: normative values with magnetic coil in 240 nerves.

This study was aimed at defining normative values of latency and amplitude of the compound muscle action potential (CMAP) from the orbicularis oculi muscle, obtained by transcranial magnetic stimulation. We evaluated the dependence of latency and amplitude on the age of the subjects, in order to calculate cut-off values for each age decade. A total of 120 healthy normal subjects, aged 15-78 years, were studied. CMAP from the orbicularis oculi muscle, pars inferior, was excited by means of transcranial magnetic stimulation of the homolateral scalp. A suitable mathematical model was developed to evaluate the mean variation of the latency and amplitude of CMAP for each age decade in the studied population. Mean values were, respectively, 4.62+/-0.40 ms for latency and 4.17+/-0.72 mV for amplitude. We found an increase in latency of about 0.12 ms for every ten years, that became 0.15 ms if referring only to subjects over 20 years, and a decrease in amplitude of 0.18 mV each ten years. Normality interval values for the latency and amplitude were calculated for each age decade. Our data, obtained in a representative population for range of age of evaluated subjects, provide normality values and variability coefficients useful for future confronting works.

High-dose intravenous immunoglobulin treatment of multiple sclerosis.

A review of the pathological basis of multiple sclerosis is presented to see whether the many immunological effects if IVIg may exert some benefit and at what level. This is probably due to the wide spectrum of interactions between IVIg and the immune system, which are analyzed in this review. Macrophage Fc receptor saturation and block, anti-idiotypic effect, reduction of endothelial cell activation and superantigen-neutralizing antibodies are probably involved in the action of IVIg in dysimmune demyelinating diseases. Furthermore, IVIg promote remyelination in virus-induced experimental encephalomyelitis. Trials on IVIg in MS demonstrated a reduction of relapse rate (RR) and appearance of gadolinium-enhancing lesions on magnetic resonance imaging. Furthermore IvIg are regarded as a promising treatment to reduce RR in post-partum period. However, studies on secondary-progressive MS failed to demonstrate an IVIg effect on disability and IVIg failed to improve stabilized visual and motor deficits in two large trials.

Autoantibodies in multiple sclerosis patients before and during IFN-beta 1b treatment: are they correlated with the occurrence of autoimmune diseases?

Autoimmune side effects, namely autoantibody (autoAb) occurrence and thyroid function alteration, have been described during interferon-beta (IFN-beta) treatment for multiple sclerosis (MS). AutoAb occurrence and autoimmune thyroid diseases are also frequently detected in MS patients free of any treatment. The aim of this study was to evaluate the relationship between IFN-beta 1b treatment, autoAb occurrence, and autoimmune diseases in MS. Thyroid and liver function and serum autoAb (antithyroid, antinuclear, anti-liver, anti-kidney microsomes, anti-smooth muscle and parietal cell antigens) occurrence were evaluated in 156 relapsing-remitting MS (RRMS) patients before and every 3 months after starting IFN-beta 1b treatment (8 MIU subcutaneously [s.c.] on alternate days). The probability of having liver or thyroid function alteration or autoAb occurrence was analyzed longitudinally with the generalized estimating equations (GEE) approach. At baseline, 16.1% of patients had autoAb. During treatment, autoAb occurred de novo in 7.2% of patients. GEE analysis showed that the probability of having autoAb at any time during IFN-beta 1b treatment did not change significantly compared with baseline. AutoAb occurring de novo rarely persisted during treatment and significantly less than those already present at baseline. Positivity for autoAb at baseline or during treatment was not correlated with the development of thyroid or liver function alteration during IFN-beta 1b treatment. Our study indicates that IFN-beta treatment is a safe treatment for MS patients, free of risk of autoimmunity and of associated liver or thyroid function alteration.

Thyroid function and anti-thyroid antibodies in MS patients screened for interferon treatment. A multicenter study.

Interferon beta (IFNB) treatment for multiple sclerosis (MS) has been associated with thyroid disorders (TD), in particular in patients with subclinical TD or anti-thyroid (AT) autoantibodies (autoAb) before starting treatment. TD and AT autoAb frequency was reported increased in MS. To determine whether MS patients have subclinical thyroid function abnormalities or anti-thyroid autoimmunity predisposing to develop TD, we performed a prospective multicenter screening of thyroid function and autoimmunity in 152 relapsing-remitting (RR) MS patients selected to receive IFNB treatment and in 437 healthy normothyroidal controls. Thyroid-related hormones and anti-thyroid microsomal antigen (anti-TMA) autoAb were tested with sensitive immunoradiometric or chromatographic assays. Cases were stratified for different progressively decreasing or increasing cutoff values of thyroid-stimulating hormone (TSH) (0.3, 0.2, 0.1, 3 and 5 mIU/l), and odds ratios (OR) with 95% confidence intervals (CI) calculated using logistic regression adjusted for gender, age, and anti-TMA autoAb positivity. The frequency of cases below or above the TSH cutoff values was not significantly different in MS patients and controls, and the risk to have an abnormal TSH level was not significantly increased in MS patients (OR ranging 0.37-0.84; CI, 0.05-3.01), even if anti-TMA autoAb positive (OR ranging 0.35-0.85; CI, 0.04-3.00). Frequencies of subclinical hypothyroidism and of anti-TMA autoAb positivity were, however, trending higher in MS men (ranging 5-7%) than in controls (3%). MS patients do not have an increased risk of subtle thyroid function abnormalities, subclinical TD, or anti-TMA autoAb positivity that may predispose to develop thyroid dysfunction during IFNB treatment. The positive trend for subclinical hypothyroidism and anti-TMA autoAb positivity, however, advises a longitudinal study of thyroid function and autoimmunity during IFNB treatment to see whether patients with baseline subclinical thyroid dysfunction develop clinically significant alteration during treatment.

Interferon-beta dose and efficacy: the OPTIMS study.

Interferon beta (IFN-beta) reduces exacerbation rates in patients with relapsing-remitting multiple sclerosis (MS), but some patients do not respond to treatment. Recent studies have shown a clear dose-response effect on the reduction of exacerbation rates, and on burden of disease accumulation and active lesion frequency seen on MRI. During treatment with 8 MIU IFN-beta we noticed a 30% rate of treatment failure. We then treated non-responders with 12 MIU IFN-beta and observed significant improvement in the clinical signs of disease activity. In order to compare the efficacy of two different doses of IFN-beta-1b, a multicenter study for the optimization of interferon for MS (OPTIMS) has been organized. The design of the study is presented here.

Terminal latency index in polyneuropathy with IgM paraproteinemia and anti-MAG antibody.

Criteria for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) are met by the polyneuropathy associated with immunoglobulin M (IgM) paraproteinemia and anti-myelin-associated glycoprotein (MAG) antibody (MAG-CIDP). However, MAG-CIDP differs from other types of CIDP, mainly in its poorer response to treatment. The utility of terminal latency index (TLI) as an electrophysiological marker for MAG-CIDP has been debated. In this study we confirmed its diagnostic usefulness and evaluated TLI threshold values for motor nerves investigated in routine nerve conduction studies. Median, ulnar, peroneal, and tibial TLIs of 11 subjects with MAG-CIDP, 18 with CIDP, and 76 healthy controls were compared, and threshold values for MAG-CIDP evaluated as the lowest value with a likelihood ratio higher than 10. Mean TLI values and TLIs of all but the peroneal nerve were significantly lower in MAG-CIDP. Median nerve TLI of 0.26 and ulnar nerve TLI of 0.33 were identified as the threshold TLI values for MAG-CIDP.

Anti-GM1 and anti-sulfatide antibodies in polyneuropathies. Threshold titers and accuracy.

OBJECTIVES: To determine threshold titers and diagnostic accuracy of anti-GM1 and anti-sulfatide antibodies (Ab) for autoimmune polyneuropathies (PN) in overall and for particular subtypes of them. MATERIALS AND METHODS: In this study 84 PN patients, 120 epileptics and 93 healthy controls' sera were tested by enzyme-linked immunosorbent assay for autoAbs and results confirmed by thin-layer chromatography. Frequencies of positive patients at increasing cut-off were compared to determine threshold titers. Accuracy was determined by Receiver Operator Characteristic analysis. RESULTS: A 1:2,000 titer for IgM anti-GM1 and a 1:4,000 titer for IgM anti-sulfatide Ab resulted to be threshold titers for autoimmune PN in overall. IgM anti-GM1 and anti-sulfatide Ab had low discriminating capacity between autoimmune PN and other PN, but good discriminating capacity between motor neuropathy (for anti-GM1 Ab) or PN in IgM-paraproteinemia or chronic painful sensory axonal PN (for anti-sulfatide Ab) and other PN. CONCLUSION: Our results suggest that testing IgM anti-GM1 or anti-sulfatide Ab is useful only for diagnostic confirmation of specific subtypes of autoimmune PN.

Does high-dose interferon beta-1b improve clinical response in more severely disabled multiple sclerosis patients?

Prospective clinical open label follow-up of 52 multiple sclerosis patients treated with interferon beta-1b. After 18 months of treatment at standard 8 million international units (MIU) dose, subcutaneously on alternate days, IFNB dose was increased to 12 MIU in ten clinically non-responder patients. Eighteen months after, mean exacerbation rate, number and severity of exacerbations and number of patients with exacerbations or requiring corticosteroid treatment significantly improved, becoming similar to those of IFNB responders, always treated with 8 MIU. Baseline EDSS score of non-responders was higher than that of responders. Frequency and severity of adverse events were trending higher and dropout frequency higher in 12 MIU IFNB-treated patients.

Autoimmune events during interferon beta-1b treatment for multiple sclerosis.

Autoimmune events, although rarely reported during interferon beta-1b (IFNB) treatment of relapsing-remitting (RR) multiple sclerosis (MS), may be more frequent than expected due to the many immunologic abnormalities associated with this disease. We report the prospective two-year follow-up of autoimmune events in 40 RR MS patients treated with IFNB and in 21 untreated MS controls. Thyroid and liver function and serum level of 12 autoantibodies (autoAbs) against organ- (thyroid, gastric, pancreatic) and non-organ-specific antigens were serially monitored. In contrast to control patients, autoAbs (anti-nuclear, -smooth muscle or -thyroid antigens) were detected in 13 IFNB-treated patients, and these were associated with thyroid or liver function alteration in many cases. Persistent autoimmune thyroid dysfunction occurred in three IFNB-treated patients, all of whom were women with a familial history of thyroid disease or baseline anti-thyroid autoAb positivity. For improvement of the MS relapse rate, thyroid dysfunction was adequately treated without stopping IFNB. Liver function alteration (17 IFNB-treated patients, associated with non-organ-specific autoAbs in four) was transient and did not require IFNB treatment to be stopped, with the exception of one patient who was already suffering from a drug-induced hepatopathy at baseline. During the IFNB treatment of MS, several autoimmune events may occur, indicating that thyroid and liver function and autoAbs must be carefully monitored.