Nerve ultrasound findings in neuropathy associated with anti-myelin-associated glycoprotein antibodies.

BACKGROUND AND PURPOSE: No systematic nerve ultrasound (US) studies on patients with neuropathy and anti-myelin-associated glycoprotein (anti-MAG) antibodies are available. PATIENTS AND METHODS: Twenty-eight patients (18 men, 10 women, mean age 69.2 ± 10.9 years; mean disease duration 6.9 years) with anti-MAG neuropathy underwent nerve US. Echotexture, nerve cross-sectional area (CSA) and intra-nerve and inter-nerve CSA variability were assessed. The frequency (number of nerves with enlarged CSA, 'enlarged nerves sum score') and distribution (proximal versus distal, arms versus legs, symmetry) of US abnormalities were considered. Controls included two groups: four patients with immunoglobulin M (IgM) paraproteinaemic neuropathy without anti-MAG antibodies and five with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with IgM paraprotein. RESULTS: In all, 26/28 patients had increased CSA (23 with at least one nerve outside entrapment sites). Intra-nerve CSA variability was abnormal in 21/28 patients (in 14 for increased nerve CSA outside entrapment sites). Inter-nerve CSA variability was abnormal in 16 patients (of whom half for CSA increase out of entrapment sites). The enlarged nerves sum score in anti-MAG neuropathy patients was greater than in MAG-negative paraproteinaemic neuropathies and lower than in CIDP. Intra-nerve variability appeared instead similar in anti-MAG and controls. No correlation was found between US findings and Inflammatory Neuropathy Cause and Treatment Group (INCAT) disability score or disease duration. DISCUSSION: Amongst the different measures to assess the US pattern (symmetry/asymmetry, proximal/distal distribution and sum score), the enlarged nerves sum score was the most useful for differentiating the three groups of patients with demyelinating neuropathies and may contribute to diagnosis in a typical cases.

Heterogeneity of root and nerve ultrasound pattern in CIDP patients.

OBJECTIVE: The few published ultrasound (US) studies on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) report diffusely increased cross-sectional area (CSA) of nerves. The data are, however, heterogeneous and correlations with clinical history or disease severity are lacking. METHODS: Thirty-four patients with CIDP underwent US nerve evaluation by two neurologists blinded to clinical data. US nerve pattern for each patient was defined by a third neurologist blinded to clinical data. Three US classes were identified based on CSA and echogenicity: large nerves with hypoechoic nerves/fascicles (class 1); large nerves with heterogeneous hypo- and hyperechoic fascicles (class 2); normal size nerve but abnormal hyperechoic array (class 3). RESULTS: In all patients, US nerve changes were observed: in most of the cases, enlarged nerves or nerve segments were observed. The three 'classes' of US nerve changes significantly correlated (R: 0.68, p<0.001) with disease duration, but not with age or Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. CONCLUSIONS: US may be of adjunctive diagnostic value in CIDP assessment. Nerve morphological changes may mirror the underlying pathophysiological mechanisms and seem to correlate with disease duration. SIGNIFICANCE: These results offer the possibility of exploring the use of US to assess CIDP disease activity and treatment.

High ultrasound variability in chronic immune-mediated neuropathies. Review of the literature and personal observations.

Chronic immune-mediated neuropathies show high clinical variability. Diagnosis is based on clinical and neurophysiological studies, but recently ultrasound (US) of peripheral nerves has been shown to provide useful morphological information. US has already been shown to crucially influence diagnosis and clinical care in entrapment neuropathies, in traumatic nerve lesions and in tumors. The role of US in the evaluation of polyneuropathies is still not clearly defined, but increasing attention has recently been focused on the immune-mediated neuropathies and specific US measures (namely the intra- and inter-nerve cross-sectional area variability) have been developed. The aim of the current paper is to make a review of the available nerve US studies and provide data from personal observations in the most common chronic immune-mediated neuropathies.

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS).

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary R-ODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.

Ultrasound assessment of oxaliplatin-induced neuropathy and correlations with neurophysiologic findings.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy is a major adverse effect of oxaliplatin (OXL) treatment. Whereas neurophysiologic study is commonly used to assess the occurrence and severity of polyneuropathies, ultrasound (US) analysis of the peripheral nerves, an emerging technique in the study of peripheral nerve diseases, has never been used in chemotherapy-induced peripheral neuropathy. PATIENTS AND METHODS: Fifteen patients (four women; 11 men; mean age, 60.1 ± 10.6 years; median, 62; range, 37-75) with colorectal cancer treated with OXL-based treatment have been clinically and neurophysiologically evaluated before and after OXL therapy. At the end of chemotherapy, all patients underwent also nerve US study at four limbs, and the findings correlated with clinical and neurophysiologic measures. RESULTS: Clinical and neurophysiological evaluation showed that 13 of 15 (86.7%) patients developed sensory axonal neuropathy, 10 of whom severe (two or more sensory nerve action potential amplitude absent and the other amplitudes decreased of ≥50%). Nerve US did not reveal decreased cross-sectional area (CSA), a reported finding in axonal neuropathies. Instead increased CSA at entrapment sites (median nerve at wrist and ulnar nerve at elbow) was found in 09/15 (60%) of patients. DISCUSSION: Sensory axonal neuropathy is a very common complication of OXL therapy, affecting almost 90% of patients. US findings of enlargement of median and ulnar nerves, mostly at entrapment sites, in patients with no history or symptoms of neuropathies at recruitment, and no neurophysiologic evidence of entrapment, may be expression of increased, OXL-induced, nerve susceptibility to mechanical damage. An ongoing prospective study will help clarify these findings.

[Spa therapy in osteoarthritis: experience in Cervia]. / La terapia termale nell'osteoartrosi: esperienza di Cervia.

AIMS: Mud-bath treatment has a relevant therapeutic activity in reducing symptoms and disabilities in rheumatic diseases, as studies on inflammation process and clinical symptomatology have shown. Objective of this study is to evaluate the efficacy of mud therapy by natural limans of Cervia on clinical parameters in patients with lumbar spine osteoarthrosis (OA). MATERIALS AND METHODS: 30 patients (20 females and 10 males) suffering from lumbar OA, diagnosed by clinical symptoms and X-Ray findings (osteophytosis, morphological changes of vertrebral somes, tightness of intervertebral spaces, alterated lumbar physiologic lordosis) were studied. All patients were examined first when recruited (T0) and after two weeks of therapy (T1). Interviews were submitted in order to estimate functional restrictions and pain. Statistical analysis was performed via t test for paired data. RESULTS: On the basis of the statistical analysis a very significant difference was demonstrated between the average values of the tests before and after the treatment. These results confirm the improvement of the symptoms concerning the pain, the articular functionality and the quality of life. CONCLUSIONS: The results of the study demonstrate the efficacy of the mud-bath treatment with natural limans of Cervia on the patients affected by lumbar spine osteoarthrosis (OA).

Neurolupus is associated with anti-ribosomal P protein antibodies: an inception cohort study.

OBJECTIVE: Serum IgG antibodies (Abs) to phosphorylated ribosomal (P ribosomal) proteins have been inconsistently associated with neuropsychiatric manifestations in systemic lupus erythematosus (SLE). Our aim was to assess whether serum IgG Abs to ribosomal P proteins are associated with neuropsychiatric SLE. PATIENTS AND METHODS: We examined an inception cohort of 219 SLE patients. Neuropsychiatric SLE manifestations were characterized using the American College of Rheumatology (ACR) definition. Serum Abs to P ribosomal proteins were searched for by immunoblotting. In a subgroup of patients, Abs were investigated also in cerebrospinal fluid (CSF). RESULTS: Abs to P ribosomal proteins were detected in 45 (21%) patients, 23 of whom (51%) with neuropsychiatric involvement. Abs to P ribosomal protein were present both in serum and CSF. Abs to P ribosomal proteins significantly correlated with psychosis (p=0.017), mononeuropathy multiplex (p=0.040), malar rash (p=0.004), serum anti-Sm Abs (p=0.042), and lupus anticoagulant (p=0.036). SLE onset age was significantly younger in patients with Abs to P ribosomal proteins. Logistic regression analysis confirmed the relationship between Abs to P ribosomal proteins and psychosis, malar rash, SLE onset age and lupus anticoagulant. CONCLUSIONS: Abs to ribosomal P proteins are associated with psychosis and might be associated with peripheral nervous system complications.

Wegener's granulomatosis confined to nervous system.

Wegener's granulomatosis (WG) is a multisystemic necrotising granulomatous vasculitis of small and medium sized vessels, that primarily involves the upper and lower respiratory tracts, lung tissues and kidneys. Serum antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker of WG. Whereas the peripheral nervous system is often involved in WG, central nervous system manifestations are reported only in 2-8%, and are rarely present at onset. We report on a patient with atypical neurological presentation of ANCA negative WG in whom the diagnosis was made only after a meningeal biopsy.

[The historical-scientific foundations of thalassotherapy: state of the art]. / Le basi storico-scientifiche della talassoterapia: stato dell'arte.

Throughout the ages the interest in the use of sea water in medicine has fluctuated from century to century and from nation to nation. In this paper, the historical development of sea medicine from the ancient Egyptians until the 20th century is given. The medical world has viewed it with different opinions, from very enthusiastic to extremely critical, and from beneficial to harmful. In the last decades, thalassotherapy is receiving renewed attention from many medical specialties and health tourists. The aim of this review is that of offer an update on the real therapeutic possibility of the thalassotherapy. However, the exact therapeutic potential of thalassotherapy still remains largely unknown. Better and more profound scientific evidence for its efficacy is therefore warranted, in particular for its effects on the musculoskeletal system and skin. The main researches belong to the activity of thalassotherapy and the clinic outcomes, namely in osteoarthritis patients, were referred.

[Fine tuning of the many regulations of quality system: the role of the quality in the thermal medicine]. / Messa a punto delle varie normative che regolano il Sistema "Qualità": il ruolo della Qualità nel sistema termale.

In the last decades, quality has imposed itself as a competitive need for firms, and also as a new normative parameter to guarantee the production process and the final product which the costumer buys. In the case of health services, the importance of quality is even greater because of the special value of this service, and the special relationship between the supplier and the costumer/patient. This relationship is often mediated by the State which has to provide the health services and the financial support for them. Thus, also in the case of Thermal Medicine, quality and its certification play a key role for the evaluation of the efficiency of the health service, and tend always more to be part of the health service accreditation process. In this article, we review the development of the idea of quality of service from the ancient Egyptian until the 20th century and we briefly recall the main European and Italian norms. We also examine the norms for the accreditation of the thermal health structures, and we review the main indicators of quality in Thermal Medicine, and the role of scientific research. Finally, we indicate that the cost of the lack of quality can be so prohibitive that the firms which do not follow the new standards, are put out of the market.

[Spa and climate therapy in chronic obstructive pulmonary diseases]. / Possibilità crenoterapiche e climatoterapiche nelle malattie ostruttive polmonari croniche.

The authors remind the main epidemiological and clinical findings of Chronic Obstructive Pulmonary Disease (COPD); the prevalence and incidence of COPD is increasing and COPD is now the IV cause of death in the world. Moreover, it is cause of increasing pharmaceutic and hospital charges. COPD has multifactorial etiology, linked to genetic and exogenous factors, as tobacco smoke, air pollution, microbial infections and cold. The GOLD guide lines of the medical therapy of the COPD are showed. The spa therapy of COPD is based on the inhalation use of mineral water, mainly sulphurous and salsojodic. Sulphurous mineral waters have vasodilating activity on vessels of bronchial mucose, improving its trophic state, and increase the production of secretory IgA and muco-ciliary clearance; they have fluidificant activity on bronchial secretion. Clinical trials showed improvement of cough, sputum and functional indexes as FEV1 and CV. Salsojodic mineral waters increase the fluidity of the bronchial mucus, muco-ciliary clearance and the trophism of the bronchial mucose. The authors remind the properties of sulphate and bicarbonate mineral waters in the spa therapy of COPD. Finally authors refer about some effects of spa therapy and climatic-environmental situations on COPD morbidity.

[Recent trends in the therapy of hepatitis C]. / Recenti orientamenti di terapia dell'epatite C.

The treatment of HCV correlated hepatitis is an important argument, because of the great incidence and prevalence of this disease. At the end of the Eighties, the IFN was the first substance used for HCV correlated hepatitis therapy. The IFN monotherapy with a dose of 3-6 MU for 6-12 months eradicates the infection in the 15% of cases, and cause an histological temporary improvement in a variable number of patients that keep the infection. In the following years, the research on evaluation of the efficacy of the recombinant interferons or interferons made with genetics engineering (IFN alpha 2a, IFN alpha 2b and IFN Consensus) has given results comparable with the results obtained with IFN alpha. Later, it started the experimentations with IFN associated to other substances, for example IFN-ribavirin combination therapy. The treatment IFN-Ribavirin eradicates the infection in 30% of the patients with the genotype 1b and in 60% with the genotype 2 or 3, while this treatment is less efficacious in the patients with the genotype 4. Recently, it started to use the PEG IFN. The pegylation is the combination of a polietylen-glicole molecule with the IFN molecule, so as to prolong its half-life and reduce the dose only one a week, with reduction of the collateral effects. Some studies has shown that the use of PEG-IFN in monotherapy could help the patients with advanced liver complaint. Successive studies are directed to show the efficacy of the PEG-IFN and ribavirin combination therapy. Recent researches put in evidence new substances, that could represent the future for HCV correlated hepatitis therapy. Between these substances we have to highlight the interleukin, the inhibitors of the viral multiplication and the inhibitors of IMPDH (Inosine monophosphate dehydrogenase). At the beginning of 2002 has made the improvement of HCV vaccine known. Actually, in the USA there are in progress human experimentations, and the production of gamma-globuline, that could be effective to prevent the infection.

[Meta-analytical study of gastrointestinal stromal tumors (GIST)]. / Studio metanalitico dei tumori stromali gastrointestinali (GIST).

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gut wall. GIST have still today controversial aspects of their histogenesis that are reflected on the classification, clinical behaviour and prognosis. The authors analyzed 14 studies observed between 2000 and 2001; also the tumors early classified as leiomyomas, leiomyosarcomas and schwannomas were included in these studies because, on the basis of immunohistochemical analysis, their cells were c-Kit positive. The GIST occurred in 728 patients with the age range of 12 days-96 years with a male predominance (59.3%). The most common symptoms were abdominal pain (25.4%) and gastrointestinal bleeding (23.4%). CT scan was the most important diagnostic technique. Surgery was the only useful treatment; in this study completeness of resection predicted for longer survival. Overall survival was between 21.4% and 88.8%; the percentage of deaths was between 11.1% and 78.5%. Distant metastases, localised in liver and lungs, and locoregional recurrences developed in a percentage between 9% and 68%.

[Fangotherapy in chronic degenerative rheumatic diseases]. / La fangoterapia nel trattamento delle malattie reumatiche croniche degenerative.

The authors remind the historical role of the mud-therapy in the care of chronic degenerative rheumoartrhopaties, namely osteoarthritis. The main researches belong activity of muds on plasmatic hormones, cytokines, endorphins; a great deal of care is devoted to evaluation of efficacy of mud therapy and relating end points. The clinic outcomes of mud therapy, namely in osteoarthritis patients, were referred. Altogether the studies stress the employ of mud therapy in the treatment of osteoarthritis, the consequences of traumas, some dismetabolic chronic arthropaties, and fibromyalgic syndromes.

[MDR (multidrug resistance) in hepatocarcinoma clinical-therapeutic implications]. / MDR (multidrug resistance) nell'epatocarcinoma: implicazioni clinico-terapeutiche.

Our purpose was to summarize current knowledge on "multidrug resistance", or MDR, an intrinsic or acquired cross resistance to a variety of structurally and functionally unrelated drugs, still representing one of the major problems in the therapy of cancer and other diseases. MDR depends on various mechanisms, the best known being the activity of ABC transport proteins, mainly Pgp, MDR1 gene product,and MRPs; but also other transporters can cause resistance, for example TAP, a peptide transporter, CFTR, cystic fibrosis transmembrane regulator, ABCG2, or breast cancer resistance protein (BCRP) and LRP, lung resistance protein. MDR has been detected in nearly all types of cancer, because it affects many organs and can occur against a wide number of drugs; it is frequent even in other diseases, such as epilepsy and HIV. We focused on MDR phenomenon in HCC, one of the commonest tumors in the world, and one of the most resistant to pharmacological treatment. This characteristic might be partly determined by a link between MDR and angiogenic phenotypes. The relationship between MDR in hepatocellular carcinoma and the effectiveness of therapeutic treatments has been particularly examined. Finally, the importance to overcome the strong chemoresistance of hepatocellular carcinoma with methods alternative to drugs, namely gene therapy, which makes use of antisense oligonucleotides and anti-MDR1 ribozymes, has been pointed out.

[Possibilities of thermal medicine in gastrointestinal functional disorders]. / Possibilità della medicina termale nei disordini funzionali gastroenterici.

The aim of this review is that of offer an update on the real therapeutic possibility of the thermal medicine in the functional gastrointestinal disorders. The functional dyspepsia, the irritable bowel syndrome, the functional constipation and the functional disorders of the biliary tract (in accordance with Roma II criteria), are the illness for which the drinking mineral waters could give a valid therapeutic support.

[Prevalence of dyspepsia in liver cirrhosis: a clinical and epidemiological investigation]. / Prevalenza della dispepsia nella cirrosi epatica. Indagine clinico-statistica.

BACKGROUND: To evaluate the prevalence and severity of dyspepsia in patients with liver cirrhosis. METHODS: A questionnaire was distributed to 33 consecutive patients suffering from liver cirrhosis (22 males and 11 females, mean age 65.5 years; 24 with post-hepatitis liver cirrhosis and 9 with alcohol- based cirrhosis) to evaluate dyspeptic symptoms. Patients receiving prolonged treatment at home with anti-acid drugs immediately prior to hospitalisation were excluded from the study. RESULTS: Twenty-eight patients complained of dyspeptic disorders. An organic cause of symptoms could not be identified in 8 patients (24.2%), whereas the following were identified as the causes of organic dyspepsia in the remaining 20 patients, in order of frequency: gastroesophageal reflux disease (55%), congestive gastropathy (40%), gastric or duodenal ulcer (30%) and gallbladder stones (35%). Lastly, a combination of at least two of these morbid conditions was found in 10 patients (50%). The severity of dyspeptic symptoms was similar in both organic and functional forms; symptoms tend to occur with moderate intensity, worsening in parallel with the aggravation of liver disease. CONCLUSIONS: Dyspepsia is a very frequent phenomenon in cirrhotic patients; it is normally sustained by an organic cause. The predominance of functional forms in liver cirrhosis is practically the same as that reported in the general population.