Evolution of Magnetic Order from the Localized to the Itinerant Limit.

Quantum materials that feature magnetic long-range order often reveal complex phase diagrams when localized electrons become mobile. In many materials magnetism is rapidly suppressed as electronic charges dissolve into the conduction band. In materials where magnetism persists, it is unclear how the magnetic properties are affected. Here we study the evolution of the magnetic structure in Nd_{1-x}Ce_{x}CoIn_{5} from the localized to the highly itinerant limit. We observe two magnetic ground states inside a heavy-fermion phase that are detached from unconventional superconductivity. The presence of two different magnetic phases provides evidence that increasing charge delocalization affects the magnetic interactions via anisotropic band hybridization.

The epidemiology of amyotrophic lateral sclerosis in the Mount Etna region: a possible pathogenic role of volcanogenic metals.

BACKGROUND AND PURPOSE: Trace elements (TEs) may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and volcanic degassing is the major natural source of TEs. Mount Etna, in the province of Catania, is the largest active volcano in Europe. Our aim was to assess the incidence of ALS in the province of Catania during 2005-2010 and its spatial distribution with respect to volcanic gas deposition. METHODS: Cases from all neurological centres of the province of Catania and of the boundary provinces were retrospectively collected. Patients who had onset during 2005-2010 and fulfilled the El Escorial revised diagnostic criteria were included. The incidence of ALS was estimated for the entire province and separately for the population living on the eastern and western flank of Mount Etna, respectively, the most and least exposed areas to volcanogenic TEs, considered as a possible risk factor for ALS. RESULTS: One hundred and twenty-six (57 men) ALS patients were enrolled. The mean annual crude incidence rate was 2.0/100 000 person-years (95% confidence interval 1.7-2.4). A higher incidence rate was found in the population living on the eastern flank compared to the western flank (2.4/100 000 and 0.9/100 000 respectively) with a relative risk of 2.75 (95% confidence interval 1.64-4.89; P < 0.001). CONCLUSIONS: The incidence of ALS in the province of Catania is close to those reported worldwide. The incidence was higher amongst the population living on the eastern flank of Mount Etna, which could be interpreted as a possible role of volcanogenic TEs. Further research on TEs and genetic factors is necessary to support this assumption.

Restless legs syndrome and multiple sclerosis: a population based case-control study in Catania, Sicily.

BACKGROUND AND PURPOSE: A population-based case-control study in the city of Catania, Sicily, was carried out to determine restless legs syndrome (RLS) prevalence and its association with multiple sclerosis (MS). METHODS: Patients were randomly selected from a cohort of MS patients resident in the study area and a group of age and sex matched controls was enrolled from the general population. RLS was diagnosed according to the International Restless Legs Syndrome Study Group criteria. RESULTS: In total, 152 MS patients and 431 controls were included in the study. A significantly higher prevalence of RLS amongst MS patients (14.5%) compared with controls (6.0%) was detected, corresponding to an almost threefold increased risk (odds ratio 2.7, 95% confidence interval 1.4-5.0) of developing RLS. Spinal cord lesions in MS patients were associated with a higher risk of RLS (odds ratio 3.7, 95% confidence interval 1.1-13.5). CONCLUSION: RLS was strongly associated with MS, with a significantly higher risk in patients presenting spinal cord lesions.

Multiple Sclerosis State of the Art (SMART): A Qualitative and Quantitative Analysis of Therapy's Adherence, Hospital Reliability's Perception, and Services Provided Quality.

The purpose of this study was to assess the adherence to therapy in patients with relapsing remitting multiple sclerosis (RR-MS) and to analyze the possible influence of factors such as hospital care and patients socioeconomic status. Two hundred eighty-five patients with RR-MS according to Mc Donald's criteria and naïve disease-modifying drugs (DMDs) naïve were enrolled. Two self-administered questionnaires addressing the management of patients at therapy prescription and the personal perception of the daily life changes caused by DMDs were administered at months 3 and 12. Full adherence, considered as correct use of the therapy prescribed, was observed in a very high percentage of subjects (97.3% and 93.9% at 3 and 12 months). The main cause for reduced adherence was single dose forgetfulness, followed by anxiety, pain at the injection site, and tiredness of "doing all injections." Nurses and neurologists of MS Center were identified as the major resource in coping with the disease at 3 and 12 months by patients. The neurologist was the health professional involved in MS management in 95% of cases and the nurse appeared to play a central role in patient training and drug administration management (50.3%).

Prevalence of patient-reported dysphagia in multiple sclerosis patients: an Italian multicenter study (using the DYMUS questionnaire).

OBJECTIVE: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with a chronic course. Dysphagia represents one of the current challenges in clinical practice for the management of MS patients. Dysphagia starts to appear in mildly impaired MS subjects (EDSS 2-3) and becomes increasingly common in the most severely disabled subjects (EDSS 8-9). The aim of the present study was to evaluate the frequency and characteristics of patient-reported dysphagia in MS patients with a multicenter study using the recently developed DYMUS (DYsphagia in MUltiple Sclerosis) questionnaire. DESIGN: Data were collected in a multi-centre, cross-sectional study using a face-to-face structured questionnaire for clinical characteristics and the DYMUS questionnaire. RESULTS: 1875 patients were interviewed. The current study has shown a correlation between patient-reported dysphagia and EDSS and disease course but not with age, gender and disease duration. Questionnaires were divided into "patient-reported dysphagia-yes" (587, 31.3%) and "patient-reported dysphagia-no" (1288, 68.7%). Compared with the patient-reported dysphagia-no group, patients in patient-reported dysphagia-yes group had higher EDSS score (mean EDSS 4.6 vs. 2.8; p<0.001) and had a longer disease duration (mean duration 13 years vs. 11 years; p<0.001), while there was no significant difference in gender (32.7% vs. 30.5% male and 67.3% vs. 69.5% female) and in age composition (46.18 vs. 42.05). CONCLUSIONS: This study represents the largest, multi-centre sample of MS patients evaluated for patient-reported dysphagia utilizing an ad-hoc questionnaire for this condition.

Botulinum toxin improves dysphagia associated with multiple sclerosis.

OBJECTIVE: To evaluate the efficacy of botulinum neurotoxin type A (BoNT/A) for severe oro-pharyngeal dysphagia associated with multiple sclerosis (MS). PATIENTS AND METHODS: BoNT/A was injected percutaneously into the hyperactive cricopharyngeal muscle of 14 dysphagic MS patients under electromyographic control. Patients were evaluated by videofluoroscopic and electromyographic examinations and by the Penetration/Aspiration Scale (PAS), at week 1, 4, 12, 16, 18, and 24 after BoNT/A injection. RESULTS: All patients showed a significant improvement in all the swallowing outcome measures. CONCLUSION: No specific treatment for oro-pharyngeal dysphagia related to MS has been described to date. Our preliminary findings suggest a potential benefit from BoNT/A treatment in MS patients with dysphagia associated with upper esophageal sphincter hyperactivity.

Validation of the DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis.

Swallowing problems can complicate the course of multiple sclerosis (MS). However, no validated questionnaire for the assessment of dysphagia in MS is currently available. We previously developed a 10-item DYsphagia in Multiple Sclerosis questionnaire (DYMUS). In the present study, this questionnaire was submitted to a validation process. Thirteen Italian MS centres took part in this research in which DYMUS was administered to 1734 consecutive MS patients during routine checkups outside relapse. The questionnaire showed very good internal consistency (Cronbach's alpha = 0.914). It was then subdivided into two subscales, both of which also showed very good internal consistency: Cronbach's alpha was 0.885 for the 'dysphagia for solids' subscale and 0.864 for the 'dysphagia for liquids' subscale. The DYMUS questionnaire was found to be an easy and reliable tool for detecting dysphagia and also for the preliminary selection of patients requiring more specific instrumental analyses, and those suitable for aspiration prevention programmes.

Headache and multiple sclerosis: a population-based case-control study in Catania, Sicily.

We carried out a population-based case-control study to evaluate the association between multiple sclerosis (MS) and headache. We had previously determined the incidence of MS during 1990-1999 in Catania, Sicily, identifying 155 incident MS patients; these subjects underwent a telephone interview using a standardized questionnaire for headache. Diagnosis and classification of headaches were made according to International Headache Society criteria (1988). A control group was selected from the general population through random digit dialling. One hundred and one (65.2%) MS patients, of the 155 identified, and 101 controls were screened for headaches. Fifty-eight (57.4%) MS patients and 38 (37.2%) controls fulfilled the diagnostic criteria of headache. A significant association between MS and headache was found with an adjusted odds ratio, estimated by logistic regression, of 2.18 (95% confidence interval 1.27, 3.93). Frequency of headaches in our MS population is higher than in the general population, supporting the hypothesis of a possible association between these two conditions.

The DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis.

Swallowing problems can be relevant, even if underestimated, in Multiple Sclerosis (MS) patients. However, no specific questionnaire for the assessment of dysphagia in MS is available. We built a questionnaire (DYsphagia in MUltiple Sclerosis, DYMUS) that was administered to 226 consecutive MS patients (168 F, 58 M, mean age 40.5 years, mean disease duration 10.1 years, mean EDSS 3.1) during control visits in four Italian MS Centres. DYMUS was abnormal in 80 cases (35%). The patients who claimed to have swallowing problems had a significantly higher mean DYMUS score that the other patients (p<0.0001). Mean DYMUS scores were significantly higher in the progressive forms (p=0.003). DYMUS values were significantly correlated to EDSS (p=0.0007). DYMUS showed a very good internal consistency (Cronbach's alpha 0.877). Factor analysis allowed us to sub-divide DYMUS in two sub-scales, 'dysphagia for solid' and 'dysphagia for liquid', both of them had a very good internal consistency (Cronbach's alpha 0.852 and 0.870 respectively). DYMUS demonstrated to be an easy and consistent tool to detect dysphagia and its main characteristics in MS. It can be used for preliminary selection of patients to submit to more specific instrumental analyses, and to direct toward programs for prevention of aspiration.

Amyloid myopathy presenting with rhabdomyolysis: evidence of complement activation.

At age of 57 years, a man experienced an episode of rhabdomyolysis. On that occasion muscle biopsy was not performed, however monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Further he developed a moderate proximal muscle weakness with CK level persistently elevated (1000-1200U/l). When he came to our observation, at age 67, a muscle biopsy revealed an amyloid myopathy and multiple myeloma was at the same time disclosed. Terminal complement complex C5b9 (membrane attack complex) deposits were found in the vessel walls and muscle fibers surface depicted by amyloid. Our case suggests to keep in mind the possibility that amyloid myopathy may begin as an isolate episode of rhabdomyolysis. The detection of complement complex C5b9 suggests that complement cascade is implicated in the muscular damage of amyloid myopathy.

Possible increasing risk of multiple sclerosis in Catania, Sicily.

OBJECTIVE: To update prevalence and incidence rates of multiple sclerosis (MS) in Catania, Italy during 1990 to 1999 and evaluate their temporal profiles to assess a possible increase in the MS risk in our study population. METHODS: We studied the frequency of MS in Catania, Italy (population of 313,110 as reported in the 2001 census). The primary sources for the case ascertainment were the neurologic and motor-rehabilitation departments, the MS centers, the Italian MS Association, private neurologists, and family doctors. We considered as prevalent and incident cases all patients who satisfied Poser's criteria for clinically definite MS (CDMS), laboratory-supported definite MS (LSDMS), clinically probable MS (CPMS), and laboratory-supported probable MS (LSPMS). RESULTS: We found 288 subjects with MS who had onset of disease before December 31, 1999 (prevalence day) in a population of 313,110 inhabitants. The prevalence rate was 92.0/100,000 (95% CI 81.8 to 103.2) and was higher in women (102.4/100,000) than in men (80.4/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 years (208.2/100,000). From 1990 to 1999, 155 patients with MS had the clinical onset of the disease. The mean annual incidence was 4.7/100,000 (95% CI 4.0 to 5.5). Age-specific incidence showed a peak in the group aged 25 to 34 years (11.7/100,000). Mean annual incidence for 5-year intervals increased from 3.9/100,000 during 1990 to 1994 to 5.5/100,000 during 1995 to 1999. CONCLUSIONS: Prevalence and incidence rates of multiple sclerosis have further increased during the last decade.

High incidence and increasing prevalence of MS in Enna (Sicily), southern Italy.

Twenty years after a first survey, a follow-up study was performed on the prevalence of MS in Enna (Sicily), southern Italy. The prevalence of definite MS rose from 53 to 120.2 per 100,000 population. The incidence of definite MS for the period 1986 to 1995 was 5.7 per 100,000 per year. The innermost part of Sicily shows an elevated prevalence of MS, second only to Sardinia in the Mediterranean area.

Pharmacogenomics of neurodegenerative diseases.

Current knowledge of sporadic degenerative disorders suggests that, despite their multifactorial etiopathogenesis, genetics plays a primary role in orchestrating the pathological events, and even dramatically changes the disease phenotype from patient to patient. Genes may act as susceptibility factors, increasing the risk of disease development, or may operate as regulatory factors, modulating the magnitude and severity of pathogenic processes or the response to drug treatment. The goal of pharmacogenomics is the application of this knowledge to elaborate more specific and effective treatments and to tailor therapies to individual patients according to their genetic profile. Here, we outline the leading theories on the etiopathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer disease, and we review the potential role of genetic variations, such as gene mutations and polymorphisms, in each context. We also suggest potential targets for new therapeutic approaches and variability factors for current treatments based on genotype features. Finally, we propose a few options of preventive therapeutic interventions in patients with a high genetic risk of disease.

Detection of Borrelia burgdorferi DNA and complement membrane attack complex deposits in the sural nerve of a patient with chronic polyneuropathy and tertiary Lyme disease.

We report a patient who developed a chronic sensory-motor polyneuropathy and a progressive myelopathy 4 years after a tick bite. An increased serum antibody titer to Borrelia burgdorferi suggested a diagnosis of Lyme neuroborreliosis, although a concomitant cervical spondylosis probably contributed to spinal cord damage. Treatment with ceftriaxone resulted in a marked improvement of neuropathic symptoms, providing indirect evidence of spirochetal infection. Search for B. burgdorferi DNA by polymerase chain reaction amplification on sural nerve confirmed the diagnosis, demonstrating that the spirochete localized in the peripheral nervous system. The presence of complement membrane attack complex deposits and macrophage infiltrates around epineurial vessels and within the endoneurium suggests that the neuropathy in our patient was immune-mediated.

IL-6 detection in multiple sclerosis brain.

By using a double-label immunohistochemistry technique, we demonstrated the presence of interleukin-6 (IL-6) in acute and chronic active plaques from the brain of six patients with multiple sclerosis (MS). IL-6 was mainly associated with astrocytes and rarely with macrophages or mononuclear infiltrating cells. The pattern of distribution for IL-6 immunoreactivity was similar to that of HLA-DR expression, but the two molecules almost never colocalized on the same cell. Our data indicate that in MS central nervous system IL-6 is predominantly located within resident glial cells which are concentrated at the sites of ongoing demyelination and immune activation. Although IL-6 exhibits several proinflammatory activities, indirect evidence suggests that the cytokine may also play an immunomodulatory role in inflammatory demyelinating disorders.

The potential role of hepatitis C virus in the pathogenesis of the neurological syndrome in chronic hepatitis C.

A 72-year-old man developed chronic sensory neuropathy (CSN) during chronic hepatitis C (HCV) infection. Neurological symptoms began one year after acute HCV hepatitis and slowly worsened over three years. No conventional cause for CSN was found. Circulating antinervous tissue antibodies (including anti-Hu) and inflammatory infiltrates in sural nerve biopsy specimens were absent. However, the presence of anti-HCV antibody and HCV-RNA in cerebrospinal fluid indicated that HCV had reached the intrathecal compartment, suggesting the direct viral involvement in the pathogenesis of CSN.

Association of polyclonal anti-GM1 IgM and anti-neurofilament antibodies with CSF oligoclonal bands in a young with amyotrophic lateral sclerosis.

INTRODUCTION: The significance of the association of motor neuron syndromes with anti-GM1 antibodies remains unclear. We report the immunological study of a juvenile case of amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Serum anti-Gm1 and anti-neurofilament antibodies were assayed by ELISA and western blotting and cerebrospinal fluid (CSF) isoelectrofocusing was performed. Immunocytochemical studies were carried out with the patient's serum and CSF on human brain and spinal cord sections. RESULTS: Serum polyclonal IgM anti-GM1, anti-neurofilament antibodies and CSF oligoclonal bands were detected. Furthermore, an in vitro production of anti-GM1 IgM was demonstrated. Immunocytochemical studies showed cytoplasm motor neuron immunostaining, due to both IgG and IgM, that substantially decreased after immunoabsorption of the serum with bovine neurofilament proteins but not with GM1-containing liposomes. No immunostaining was obtained with CSF. Immunosuppressive treatment with cyclophosphamide and two cycles of plasma exchanges lowered anti-GM1 antibody levels, but did not determine any clinical improvement. CONCLUSION: To our knowledge, this is the first report of ALS, associated with circulating levels and in vitro production of polyclonal IgM anti-GM1, anti-neurofilament antibodies and CSF oligoclonal bands. These findings suggest the occurrence in our patients of an autoimmune process that could be involved in the pathogenesis of ALS.

Intrathecal synthesis of anti-myelin basic protein IgG in HIV-1+ patients.

Human immunodeficiency virus type 1 (HIV-1)-infected individuals frequently develop a broad spectrum of neurological syndromes, classified as HIV-1-associated cognitive/motor complex. Diffuse demyelination of hemispheric white matter is a commonly observed in HIV-1 infected brain, but the events leading to myelin destruction are still obscure. Since oligodendrocyte infection by HIV-1 is not proven as yet, myelin damage in HIV-1 infection may result from indirect mechanisms such as the excessive release of myelinotoxic substances or the triggering of autoimmune responses directed to myelin constituents. To verify the latter hypothesis, we searched for elevated anti-myelin basic protein (MBP) IgG levels in the cerebrospinal fluid (CSF) and serum of 25 patients with HIV-1 infection, 12 with multiple sclerosis (MS), and 9 with non-inflammatory neurological diseases (NIND). CSF, but not serum, anti-MBP IgG levels were more frequently elevated in HIV-1+ (16/25, 64%) than in MS (3/12, 25%) or NIND (0/9) patients. By using the anti-MBP IgG index, the anti-MBP IgG antibody specificity index (ASI), and the search for anti-MBP oligoclonal IgG, we ascertained that anti-MBP IgG were produced within the CNS in 13 of 25 (52%) HIV-1+, in 6 of 12 (50%) MS, and in none of NIND patients. The incidence of increased CSF anti-MBP IgG levels was higher among HIV-1+ patients at stage II-III (4/4, 100%) or at stage IV B (7/9, 78%) than among those at stage IV C-IV D (5/12, 42%). Although our data indicate that intrathecal anti-MBP IgG may occur early during HIV-1 infection and that they are more common in patients with HIV-1-associated cognitive/motor complex, the possible demyelinating role of these antibodies remains to be demonstrated.