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AimsThe aims of this study was to report anatomical changes of the ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thickness, and macular volume in patients with multiple sclerosis (MS). We also investigated the correlation between anatomical and functional changes in terms of visual acuity and macular sensitivity investigated and visual fields.MethodsProspective comparative study included 105 eyes of 53 consecutive patients. The patients were divided into two groups: group A included 56 eyes of 28 patients with diagnosis of MS; group B involved 49 eyes of 25 healthy patients. The examination included Goldmann tonometry, biomicroscopic and fundus oculi examination, retinography, GCC examination, circumpapillary RNFL (cpRNFL), and macular volume. The functional test included measurement of best-corrected visual acuity (BCVA), visual field, and MP.ResultsMS group showed a significant reduced GCC, cpRNFL, macular volume, BCVA, visual field, and macular sensitivity compared with the control group (P

The energy mobility method is presented and applied both numerically and experimentally to thin plates of high modal density. The energy mobility is defined as the ratio of the frequency averaged quadratic velocity at one point of a structure to the frequency averaged active power injected at one point of the structure. It can be calculated using only classic input and transfer mobilities. The property of energy additivity of the contributions of several external loads is shown to be a good approximation in the case of a single structure. To quantify the approximations on typical structures one is interested in, numerical simulations are presented on plates. A good agreement is found between the predictions using the energy mobility and the exact calculations. An experiment conducted on a plate with a real excitation confirms that the prediction of the energy mobility approach can be quite satisfactory. Finally, a remarkable property for the energy mobility (contrary to standard mobility) is noted: the insensitivity to the presence of a mass heterogeneity at driving points. This property allows one to simplify considerably the characterization of industrial structures that have in general a lot of heterogeneities. The energy mobility concept is further applied to the vibrational behaviour of an assembly. For each subsystem the connection is described by adding injected power and coupling power into the energy additivity. The equality of the frequency averaged quadratic velocity and the power flow balance at each coupling point allows one to calculate the coupling power at connection points with energy mobilities of uncoupled subsystems. A system of two plates has been used to compare the energy mobility calculation and the exact one given by the classic mobility method. The comparison shows that a connectivity factor must be introduced to keep the same formalism generally used with classic mobilities. A generalized definition for the energy mobility is then established.

Freezing of speech (FoS) and other repetitive speech behaviours can frequently occur in parkinsonian syndromes, worsening the efficacy of language functioning, hampering social interactions, and thus reducing quality of life. Pharmacological treatment are ineffective and other interventions have not specifically developed so far.The aim of this paper was to test the efficacy on a pilot rehabilitation program for freezing of speech based on cueing.Outpatient clinic.Single-case.We developed a pilot rehabilitation program based on visual, auditory and sensory cueing. The patient underwent the protocol for a 6-month period (1-hour sessions, 3 times weekly). Perceptual analyses of his speech were performed before and after the rehabilitation program by to different blinded reviewers.There has been a reduction of FoS and other iterative speech episodes. Intelligibility also improved according to both the patient and his relatives.Our preliminary results show that visual, auditory and sensory cueing can be effective to prevent and overcome FoS episodes. Possible underlying mechanisms of the improvement are discussed.Rehabilitation programs based on cueing should be considered and offered in Parkinsonian patients exhibiting FoS or other iterative speech phenomena.

The work describes an analytical procedure that allows the quantitative determination by gas-chromatography of the concentration of the components of the essentil oils in the extracts and in the lemon liquors. This would allow to standardize the preparation of the liquors by knowing the concentration of the essential oils responsible for the aroma in the lemon liquor. The results are highly reproducible and analitically verified.

No head-to-head study has been performed yet to assess whether natalizumab is more effective than classical immunomodulators in multiple sclerosis (MS).To retrospectively compare the efficacy of natalizumab vs IFN beta 1a SC (44 ??g; Rebif(®) ) on clinical and radiological findings in two matched cohorts of patients with MS.We retrospectively enrolled two cohorts of 42 patients (F/M: 35/7) with relapsing-remitting multiple sclerosis treated with natalizumab or IFN beta 1a for at least 12 consecutive months. Outcome measures were annualized relapse rate (ARR), changes in expanded disability status scale (EDSS) score, and number of contrast-enhancing lesions (CELs) at magnetic resonance imaging (MRI).In both groups, the ARR in the 12 months of treatment was lower than in the 12 months before therapy (0.24 vs 1.50 in natalizumab-treated group, P < 0.0000; 0.55 vs 1.10 in IFN beta 1a-treated group, P = 0.0006), being the effect of natalizumab significantly stronger (P = 0.0125). EDSS reduction was significantly different between the two groups in favor of natalizumab (P = 0.0018). The frequency and number of CELs per patient were decreased in both groups. In the second year, the treatment affected ARR and EDSS progression in the two groups of patients similarly to the first year, whereas number of CELs decreased more significantly in natalizumab group (P = 0.008).After 12 and 24 months of therapy, natalizumab was more effective than IFN beta 1a SC on both disease activity and disability progression. Prospective head-to-head studies would be helpful to further evaluate the differences observed in the MRI outcomes.

Cognitive dysfunction occurs in patients suffering from multiple sclerosis also at the beginning of disease. This impairment has clinical relevance during progression of disease and has major impact on social functioning. In this critical review we take into account the cognitive and emotional-behavioural changes usually observed in multiple sclerosis and we discuss these aspects considering recent studies using functional imaging approach.

Objective: To evaluate the incidence and the prevalence of neutralising antibodies (NABs) to three interferon beta (IFNβ) products in patients with multiple sclerosis (MS). Methods: Sera were tested from 125 patients with relapsing-remitting MS. Patients were treated with IFNβ-1b (Betaferon, n = 29) 8 MIU subcutaneously every other day, IFNβ-1a (Avonex, n = 44) 30 µg intramuscularly once weekly, or IFNβ-1a (Rebif, n = 36) 22 µg subcutaneously three times weekly for 6 to 18 months. An additional 16 patients were treated with Rebif 22 µg intramuscularly once or twice weekly. NABs were assessed using the cytopathic effect assay before treatment and every three months during treatment. Patients with two or more consecutive positive samples were considered to be persistent NAB positive (NAB+). Results: At baseline, no patients were NAB+. NABs developed during the first three months of treatment and continued to develop until month 18. Over 18 months of treatment, the risk of being persistent NAB+ was 31% for Betaferon, 15% for Rebif, and 2% for Avonex (Betaferon versus Avonex, p = 0.001; Betaferon versus Rebif, p = 0.19; Rebif versus Avonex, p = 0.04). In all patients with one or more NAB+ samples, the risk of becoming NAB+ was 38% for Betaferon, 18% for Rebif, and 7% for Avonex (Betaferon versus Avonex, p = 0.0007; Betaferon versus Rebif, p = 0.10; Rebif versus Avonex, p = 0.07). At month 18, the prevalence of persistent NAB+ patients was 31.6% for Betaferon, 18.7% for Rebif, and 4% for Avonex. Numbers of NAB+ patients observed were similar with intramuscular Rebif and with subcutaneous Rebif. Conclusion: The three IFNβ preparations have different degrees of immunogenicity, with Betaferon producing the highest incidence of NABs and Avonex the lowest. These differences should be considered by neurologists when selecting treatment for their patients with MS because NABs can reduce both bioavailability and clinical efficacy of IFNβ.

We read with interest the report by Birnbaum et al.1 They report results that differ from multiple studies testing interferon beta (IFNΒ) and statin combination therapy in patients with multiple sclerosis (MS). We completed a 12-month study of 10 patients with clinically isolated syndrome (CIS) suggestive of MS in which simvastatin was added in a high dose (80 mg) to an IFNΒ-1a weekly intramuscular therapy in a placebo-controlled approach. We reported that combination therapy was safe and well tolerated in this pilot study. All patients remained clinically stable.2 Our second ongoing placebo-controlled clinical trial in patients with CIS testing high-dose IFNΒ-1a and high-dose atorvastatin (80 mg) combination therapy has enrolled 30 patients, 14 of whom completed a 12-month treatment. The treatment was well tolerated, and only three patients whose assignment is still blinded had clinical relapse.3 Our in vitro Affymetrix gene expression study on peripheral blood mononuclear cells derived from 15 patients with CIS before treatment onset and 7 matched healthy controls did not show inhibition of IFNΒ-induced genes in cultures co-treated with simvastatin.2 Similarly, interim analysis of a SIMCOMBIN study that has reported data on 47 patients randomized to IFNΒ-1a alone or to a combination of IFNΒ-1a with simvastatin (80 mg daily) reported a comparable annualized relapse rate and the expression of IFNΒ biomarkers in both treatment groups.4 A gene expression study by Rudick et al.5 in 40 patients treated with both IFNΒ-1a and 20 mg of simvastatin found no evidence that statins antagonize the IFNΒ effects. All the above-mentioned studies have used high-dose statins in combination with IFNΒ. The above results are consistent with the open-label baseline-to-treatment study by Friedmann et al.,6 who reported a significant decrease in the number and volume of Gd-enhancing …

The concept of energetic mobility is presented; its use on a single structure and its use for an approximate prediction of the exchanged powers and of the local energies after rigid coupling, on an assembly is exposed. The concept of frequency averaged active power source is also proposed. Numerical simulations illustrate this method for two different homogeneous and heterogeneous substructures rigidly linked at several points.

Cloricromen is a new drug that inhibits platelet aggregation in man and in experimental thrombosis. Twenty patients with a history of atherothrombotic stroke received cloricromen (100 mg, twice daily) for 30 days in order to evaluate its effects on plasma fibrinogen, antithrombin III, and other variables of the haemostatic system. A statistically significant decrease in the prothrombin time ( P < 0.01) was found only after 30 days of therapy. This decrease was transient and disappeared 15 days after the end of treatment. No statistically significant changes in plasma fibrinogen levels, antithrombin III, partial thromboplastin time, or platelet count were observed compared with baseline values. No side-effects were reported. This study did not reveal an effect of cloricromen on coagulative variables in patients with cerebrovascular occlusive disease.

An "in vivo" diagnosis of progressive multifocal leukoencephalopathy (PML), a neurological opportunistic viral infection in AIDS patients, can be made only by brain biopsy. In order to identify viral particles, we examined the cerebrospinal fluid (CSF) of 15 AIDS patients with focal neurological signs by electron microscopy using negative staining technique. In 2 out of 3 patients with clinical and neuroradiological presumptive diagnosis of PML, the CSF examination revealed papova-like viral particles. Our results support the hypothesis that the severe cell-mediated immunodeficiency reactivates papovavirus from a latent state in the brain, leading to PML. Therefore, the CSF study by negative staining might be a useful test for an "in vivo" diagnosis of PML.

Antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) are regarded as important risk factors for ischemic stroke and transient ischemic attacks in young subjects. In fact the interaction of these antibodies with phospholipid may impair the coagulation system at several steps, promoting thrombosis. A variety of therapeutic strategies including corticosteroids, immunosuppressive drugs, antiplatelet agents and anticoagulants have been prescribed in stroke patients with aPLs, but the efficacy of these drugs has not been established yet.

A 25-year-old-healthy man, with previous history of parenteral drug abuse, developed a left homonymous hemianopsia. Computed tomographic scanning showed a single ring enhancing lesion in the right parieto-occipital area. After the demonstration of seropositivity for human immunodeficiency virus and high serum immunoglobulin G antibody titer against Toxoplasma gondii, a diagnosis of cerebral toxoplasmosis in an AIDS patient was made. An isolated visual field defect revealing cerebral toxoplasmosis may be the first presentation of AIDS. Opportunistic cerebral lesions should be always considered in subjects at risk for AIDS who present focal neurological signs.

Cerebral toxoplasmosis is the most common cause of focal CNS disease complicating AIDS and its incidence ranges from 3% to 40% of such patients. This opportunistic infection is generally due to reactivation of chronic toxoplasmosis as a consequence of severe immune deficiency. We present the clinical, neuroradiological and immunological findings of 15 AIDS patients with cerebral toxoplasmosis. All patients had focal neurological signs. CT-scan (13 cases) and NMR (2 cases) showed single or multiple mass lesions and edema. Serum IgG anti-Toxoplasma antibodies were positive in 14 patients; CSF specific IgG were positive in 5 out of 7 studied patients, while serum and CSF specific IgM were negative in all subjects. The intrathecal synthesis of anti-Toxoplasma antibodies were high in all 7 patients. A presumptive diagnosis of cerebral toxoplasmosis is based on the focal cerebral signs and neuroradiological findings. It is more frequently confirmed by the improvement of the clinical and neuroradiological picture during the treatment with pyrimethamine-sulphadiazine or clindamycin.

The AA. have considered the incidence of some primitive reflexes in the "normal" old people. 120 subjects have been examined (60 M and 60 F) between the 70 to 90 age-group. The patients have been selected on the basis of the absence of neurologic disorders, psychiatric and systematic or dysmetabolic diseases. All the subjects undergo a standard neurologic examination. Results show that the examined reflexes can be present in normal old people. These signs seem to be related to the physiological ageing of the nervous system.

The authors report three cases of AIDS presenting with psychiatric symptoms. In two cases the initial symptoms were behavioral disorders and grandiose delusion; in the third case, which started with depression, an opportunistic infection of the central nervous system was diagnosed.

A case of idiopathic hypereosinophilic syndrome (HES) is reported. The disease started at the age of 31, with polyneuropathic-like symptoms and disorders of the gastrointestinal tract. Hypereosinophilia and leukocytosis were observed. Instrumental investigation of the digestive tract showed esophagitis, a peptic ulceration, signs of chronic rectocolitis. Charcot-Leyden crystals were present in feces. Peripheral nervous system changes were seen with EMG and nerve conduction studies. Muscle biopsy findings were in agreement with the electrophysiological data and showed inflammatory abnormalities. Qualitative histology and teased nerve fiber studies of sural nerve indicated axonal degeneration. Protein substances derived from eosinophils degranulation may account for the disturbances observed in various systems and organs.

A trial was carried out on 30 patients with cerebrovascular disease to evaluate the effect of indobufen, a new antiplatelet drug, on some platelet functions and coagulation, and its tolerance, after 12-months' treatment. From the results of the present study it appears that 2 hours after administration indobufen was able to reduce platelet aggregation induced by ADP, platelet adhesiveness, circulating platelet aggregates, and to increase bleeding time. These differences remained constant throughout the treatment period. Except in 3 patients, between the 8th and 12th months, who suffered an ischaemic attack with no aftermaths, no cerebrovascular ischaemic attacks occurred during indobufen treatment. No side-effects were observed. The data indicate that indobufen is a well-tolerated drug in all situations requiring antiplatelet treatment.

Employing optical density methods, platelet aggregation in response to increasing concentration of ADP was tested in 24 patients with migraine and 15 controls. The migraine patients don't demonstrate platelet hyperaggregability when compared with controls. Platelet aggregate ratio (P.A.R.) was measured in 13 patients and 15 controls by the method of Wu and Hoak: a significant difference was found between and controls. The hyperaggregability found here, even if only for the P.A.R., may help explain the increased incidence of stroke and heart attack in migraine patients that has been reported elsewhere.

Background Temporins are small antimicrobial peptides secreted by the Rana temporaria showing mainly activity against Gram-positive bacteria. However, different members of the temporin family, such as Temporin B, act in synergy also against Gram-negative bacteria. With the aim to develop a peptide with a wide spectrum of antimicrobial activity we designed and analyzed a series of Temporin B analogs. Methods Peptides were initially obtained by Ala scanning on Temporin B sequence; antimicrobial activity tests allowed to identify the TB-G6A sequence, which was further optimized by increasing the peptide positive charge (TB-KKG6A). Interactions of this active peptide with the LPS of E. coli were investigated by CD, fluorescence and NMR. Results TB-KKG6A is active against Gram-positive and Gram-negative bacteria at low concentrations. The peptide strongly interacts with the LPS of Gram-negative bacteria and folds upon interaction into a kinked helix. Conclusion Our results show that it is possible to widen the activity spectrum of an antimicrobial peptide by subtle changes of the primary structure. TB-KKG6A, having a simple composition, a broad spectrum of antimicrobial activity and a very low hemolytic activity, is a promising candidate for the design of novel antimicrobial peptides. General significance The activity of antimicrobial peptides is strongly related to the ability of the peptide to interact and break the bacterial membrane. Our studies on TB-KKG6A indicate that efficient interactions with LPS can be achieved when the peptide is not perfectly amphipathic, since this feature seems to help the toroidal pore formation process. © 2013 Elsevier B.V. Background Temporins are small antimicrobial peptides secreted by the Rana temporaria showing mainly activity against Gram-positive bacteria. However, different members of the temporin family, such as Temporin B, act in synergy also against Gram-negative bacteria. With the aim to develop a peptide with a wide spectrum of antimicrobial activity we designed and analyzed a series of Temporin B analogs. Methods Peptides were initially obtained by Ala scanning on Temporin B sequence; antimicrobial activity tests allowed to identify the TB-G6A sequence, which was further optimized by increasing the peptide positive charge (TB-KKG6A). Interactions of this active peptide with the LPS of E. coli were investigated by CD, fluorescence and NMR. Results TB-KKG6A is active against Gram-positive and Gram-negative bacteria at low concentrations. The peptide strongly interacts with the LPS of Gram-negative bacteria and folds upon interaction into a kinked helix. Conclusion Our results show that it is possible to widen the activity spectrum of an antimicrobial peptide by subtle changes of the primary structure. TB-KKG6A, having a simple composition, a broad spectrum of antimicrobial activity and a very low hemolytic activity, is a promising candidate for the design of novel antimicrobial peptides. General significance The activity of antimicrobial peptides is strongly related to the ability of the peptide to interact and break the bacterial membrane. Our studies on TB-KKG6A indicate that efficient interactions with LPS can be achieved when the peptide is not perfectly amphipathic, since this feature seems to help the toroidal pore formation process. © 2013 Elsevier B.V.

OBJECTIVES: Approved multiple sclerosis (MS) treatments include subcutaneous and intramuscular interferon beta (IFN-β) Patient satisfaction during long-term IFN-β treatment is crucial. This study investigated the satisfaction of patients with relapsing-remitting MS treated with IFN-β-1a (Rebif) by the autoinjection system, Rebiject. MATERIALS AND METHODS: This prospective observational study recruited subjects with relapsing-remitting MS (n = 76) from 19 neurological centers in Italy who were eligible for subcutaneous IFN-β-1a treatment either as a first immunomodulatory therapy or as a switch from other treatments. Patients received IFN-β-1a 44 μg 3 times weekly via the Rebiject system. A questionnaire on the use of Rebiject and the most common adverse effects related to IFN-β-1a administration was completed monthly under the supervision of trained nurses. RESULTS: Satisfaction with treatment was reported by 80.2% of patients who received at least 1 dose. Advantages reported for the Rebiject system included its convenience (53% of all patients), ease of use (25%), reduced trauma and pain (11% and 6%, respectively), and reduced local skin reactions (5%). No significant changes from baseline were observed regarding the frequency or severity of local reactions. CONCLUSIONS: During the 1-year observation of this small cohort, most patients considered the Rebiject system to be convenient, with a third of the patients feeling that the system was easier to use than conventional procedures. Rebiject was also associated with less pain and trauma in some patients. Use of Rebiject may facilitate IFN-β-1a administration and may lead to an increase in compliance and adherence, thus increasing the effectiveness of treatment. © 2008 Lippincott Williams & Wilkins, Inc.

A young Italian woman with a POEMS syndrome is described. The patient had a plasma cell dyscrasia without clinical or laboratory evidence of multiple myeloma. The phenotypic analysis of bone marrow cells and peripheral blood lymphocytes revealed a normal pattern. The immunological study of CSF showed high levels of interleukin-6, whereas this cytokine was not detectable in the serum. Electrophysiological studies and sural nerve biopsy showed a mixed, demyelinating-axonal sensorimotor neuropathy with marked loss of large myelinated fibres. Long-term treatment with prednisone gave some clinical improvement.