bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 2
Authors: Bersano A , Carpo M , Cappellari A , Nobile‐Orazio E
Published: October 2010

Progressive brachial and lumbosacral radiculoplexopathies are well known, though infrequent, delayed complications of local irradiation. They present as slowly progressive, generally bilateral but asymmetric, limb weakness mainly affecting distal muscles. The pathogenesis is unknown although some authors supposed an autoimmune process or radio‐induced DNA changes. No treatment for this disease is currently available even if some benefits, though transient, have been reported after steroid treatment and more recently, high‐dose immunoglobulins (IVIg), suggesting a possible immune‐mediated pathogenesis. We previously reported on the beneficial effect of immunotherapies in two patients with postirradiation motor radiculoplexopathy. The first patient had a severe motor lumbosacral radiculoplexopathy starting 20 years after local radiotherapy for seminoma. He became able to walk and run with less waddling and to climb stairs without support after treatment with high‐dose intravenous steroids. The other patient had severe left brachial and bilateral lumbosacral plexopathies presenting 12 years after toracoascellar and lumbar irradiation for a Hodgkin lymphoma. She improved her right leg strength after one course of IVIg. After one year of continuous steroid therapy the first patient started to progressively deteriorate notwithstanding the subsequent administration of IVIg, resumed courses of steroids, plasma exchanges and azathioprine. The second patient, after one year of continuous IVIg treatment which led to stabilization without further improvement, was treated with high‐dose intravenous steroids and plasma exchange, with a marginal and transient amelioration followed by progressive worsening that was not halted by the resumption of IVIg. Both patients now suspended any therapy. In conclusion, in both our patients, immune therapies only induced a transient and short‐term benefit but did not affect the overall progression of the disease. These findings suggest that even if an immune or inflammatory component, possibly triggered by radiation, may be present in this condition, it does not probably represent the bulk of the pathological process.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 3
Authors: Terenghi F , Allaria S , Nobile‐Orazio E
Published: October 2010

Intravenous immunoglobulins (IVIg) are successfully used as immunomodulatory therapy in patients with multifocal motor neuropathy (MMN) but their mechanism of action remains unknown. An anti‐idiotypic block of pathogenic autoantibodies has been often postulated even if other possible mechanisms, including a modulation of the release of various cytokines, have been proposed. To evaluate the expression of cytokines in patients with MMN and their possible modulation by IVIg, we determined circulating levels of TNFα, INFγ, IL2, IL4, IL10, and IL12 by ELISA in serum samples of 17 patients with MMN and compared them with 12 patients with amyotrophic lateral sclerosis (ALS), 12 with multiple sclerosis (MS), 6 with chronic inflammatory demyelinating polyneuropathy (CIDP), 5 with myasthenia gravis (MG) and 12 healthy controls (NS). Comparable levels of INFγ, IL2, IL4, IL10 and IL12 were detected in patients’ sera and controls. Even if TNFα levels did not differ significantly among patients’ groups, they were higher than in any healthy control (mean ± SD 1.2 ± 0.5 pg/ml, range 0.7–2.4 pg/ml), in 12 (70%) MMN patients (mean ± SD 3.6 ± 1.9 pg/ml; range 0.2–7.5 pg/ml), all ALS, 3 MS (25%), 2 CIDP (40%) and 2 MG (40%). We then measured the concentration of TNFα before and after IVIg therapy in 9 MMN and 2 ALS patients. In all but one MMN patients, circulating levels of TNFα slightly increased after treatment with IVIg (mean values 4.3 vs. 7.2 pg/ml) and decreased 3 weeks after therapy while in both ALS patients they decreased or remained unchanged. No detectable level of TNFα was found in IVIg preparation. This study shows that, similarly to what previously reported in other autoimmune neuropathy as GBS and CIDP, TNFα serum levels are slightly increased in MMN but, at odds with what reported in these disease, their concentration tend to increase parallel to clinical improvement after IVIg therapy. Further studies are necessary to clarify the pathogenetic implication of this finding and in particular whether a possible deviation from a presumably Th2 to a Th1 immune response may help explaining the effect of IVIg in MMN.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 5
Authors: Provitera V , Nolano M , Stancanelli A , Di Caprio G , Crisci C , Santoro L
Published: October 2010

We studied the effect of chronic compression of median nerve at wrist on cutaneous innervation. Two‐mm punch biopsies were obtained from third fingertip in 40 patients (32 female and 8 male, age range 30–74 years) with carpal tunnel syndrome. Patients with diabetes and other metabolic or endocrinological disorders or with electrophysiological findings of a diffuse neuropathy were excluded. By means of immunohistochemical techniques and confocal microscopy we counted epidermal nerve fibers, Meissner corpuscles and myelinated papillary endings. All patients underwent electrophysiological study and quantitative sensory testing using Semmes‐Weinstein monofilaments for tactile threshold and Medoc TSA II Neurosensory analyzer for thermal threshold evaluation. Morphological and functional data were compared with age and sex matched controls. We observed abnormalities of epidermal nerve fibers, mechanoreceptors and their myelinated afferents in all patients. These abnormalities ranged from mild to marked and appeared more severe in patients with a longer disease duration and a slower conduction velocity along the median nerve.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 6
Authors: Sandroni P , Wijdicks EFM
Published: October 2010

Guillain‐Barre syndrome (GBS) is a monophasic illness. Early nadir and lack of multiple relapses have differentiated it from the chronic form (CIDP). We present a case whose unusual course overlaps both disorders. A 71‐year‐old man presented with paresthesiae and weakness evolving over 1‐week period, 2 weeks after an upper respiratory infection. Spinal fluid analysis and electrophysiologic findings supported the clinical diagnosis of GBS. He was treated with a 5‐day course of IVIG with rapid, almost complete recovery over the following 10 days. Four weeks later, his symptoms recurred. Another dose of IVIG produced rapid but transient improvement. He was started on oral steroids but continued to deteriorate. Clinical and laboratory reevaluation confirmed the presence of an inflammatory polyradiculopathy; IVIG was resumed. Over the following 3 months, his clinical course was characterized by 3 increasingly severe deteriorations, the last one to quadriplegia, severe bulbar dysfunction requiring tracheostomy and PEG placement, ophthalmoplegia and autonomic dysfunction. Transient improvements occurred between these relapses. Aggressive treatment, which included IVIG, plasma exchange, IV steroids and IV cyclophosphamide, did not produce sustained benefit. He remained pseudo‐locked‐in for 10 days. Another 5‐day IVIG course was completed; he began to improve and continued to do so over the following 5 weeks. The nadir of GBS is usually reached within 4 weeks. Treatment fluctuations usually occur within the first weeks, and relapse during the recovery phase is often limited and isolated. Multiple relapses until a defined nadir are highly uncommon. The bulbar and cranial nerve involvement, rapidity of the relapses, dysautonomia, need for mechanical ventilation, and improving electrophysiology all argue against the diagnosis of CIDP. It remains unknown whether repeated doses of IVIG could change the natural course of this disease leading to such an unusual temporal profile.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 7
Authors: Moscato G , Maritato P , Calabrese R , Nucciarone B , Borghetti D , Baglini O , Siciliano G , Sartucci F
Published: October 2010

The pathological hallmark of amyotrophic lateral sclerosis (ALS) is the progressive death of upper and lower motor neurons, leading to a clinical pictures mainly characterized by weakness, muscle wasting, brisk reflexes and Babinski sign. Routine electromyographic and electroneurographic studies are mandatory to a correct diagnosis but are unable to precisely quantify the pathological changes in the motor unit. Motor unit number estimation (MUNE) is a recent neurophysiological technique that allows to estimate number and amplitude of motor units in single muscles in order to assess the severity of ALS and to follow‐up the progression of the disease. We applied this technique in 15 patients (12 male and 3 female; mean age ± SD: 65.7 ± 9.5 yrs, range 45–82), affected by definite or probable ALS according to El Escorial Criteria, and in 11 healthy subjects (4 male and 7 female; mean age ± SD: 63.7 ± 8.2 yrs, range 50–76), in order to assess changes in motor unit features of abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. We found a significant difference (p < 0.05) in the mean number of motor units between the two groups: 75 in ADM and 51,8 in TA in the ALS cohort vs. 283,5 in ADM and 96,9 in the healthy subjects. Conversely, the differences in the mean and maximal area between the two groups did not reach the statistical significance (ALS patients: max area 34.7 mVms, mean area 1.9 mVms; healthy subjects: max area 18.2 mVms, mean area 0.9 mVms). Our preliminary results confirm that MUNE is able to quantify the pathological changes in motor unit parameter and represents an adequate follow‐up tool for disease progression and effectiveness of pharmacological treatment.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 10
Authors: Vinci P , Perelli SL , Martini D
Published: October 2010

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder due to a chromosomal deletion of region containing PMP‐22 gene or point mutations causing loss‐of‐function of PMP‐22. HNPP usually presents with acute nerve paresis following mild trauma or compression, or as a chronic demyelinating neuropathy mimicking CMT1A. We describe a family composed by a woman (I‐1), her 3 young children (II‐1, II‐2, III‐3) and her sister (I‐2). All patients showed weakness in flexor hallucis brevis and lumbricales muscles, with consequent poor stabilization of the metatarsophalangeal joints and toe hyperextension by the long toe extensors. I‐1 (35 y/o) complained of short episodes of numbness, pain and weakness associated to mild traumas and postures since the age of 12. She traveled often and got easily tired. Her leg‐sole angle during active dorsiflexion (LS) was 95 because of forefootdrop. She had varus heels, curled toes, hyperextended knees, antiverted pelvis, passive foot dorsiflexion (PFD), and reduced hip external rotation (ER). I‐2 (38 y/o) had severe toe deformities requiring surgery, varus heels and LS = 93. II‐1 (male, 10 y/o) is asymptomatic. His LS was 85, whereas hip ER was reduced. II‐2 (male, 6 y/o) complained of pain in the calves, soles, and behind the knees. He trips 5/day, falls 1/day and runs clumsily. His LS was 82, with hyperextended knees (8) and markedly reduced hip ER. II‐3 (female, 4 y/o) had the same picture of II‐2. Her LS was 85, PFD was reduced (7), hip ER reduced, and pelvis antiverted. In this patients, rehabilitation included proper shoes and foot orthoses, standing exercises on a table oscillating on the sagittal plane to recover ankle dorsiflexion and prevent knee hyperextension, active exercises to recover hip ER, postural and ambulation training. We expect that an early treatment of mild abnormalities presented by the children can prevent them from developing severe deformities and functional impairment.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 11
Authors: Melli G , Chaudhry V , Dorman T , Cornblath DR
Published: October 2010

Nerve injuries associated with surgical operations are well recognized and described in literature. Ulnar neuropathy, brachial plexus, and lumbosacral roots injuries are the most frequent as shown by two large reviews on anesthesia‐related nerve damage from the American Society of Anesthesiologists closed claims study (Kroll DA 1990, Cheney FW 1999). Several factors such as section, compression, traction, and ischemia, contribute to the nerve injuries but the exact mechanism(s) in an individual case often is unclear. We describe a case of perioperative bilateral median neuropathy at the distal forearm, an uncommon site of nerve injury, which we ascribe to demyelinative conduction block secondary to nerve compression. Nerve conduction studies precisely localized the area of abnormality. There is a limited understanding of the relationships between conventional perioperative care and the genesis of peripheral nerve lesions. As a result, there is a lack of agreement in literature on the correct standards for positioning the patient during anesthesia. In selected cases nerve conduction studies at the onset of symptoms may provide insights into localization, mechanism and prognosis of nerve lesions. We believe that a timely and proper electrophysiological study may be helpful for understanding the perioperative nerve injuries as well as for determining the best preventive strategies.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 13
Authors: Conti G , Rostami A , Scarpini E , Baron PL , Galimberti D , Scarlato G , Palumbo C , De Pol A
Published: October 2010

In the nervous system nitric oxide (NO) has been involved as a regulatory molecule in several physiological and pathological events, such as cerebral microcirculation, synaptic plasticity, neural damage, and neuroprotection. The activation of the three isoforms of the enzyme nitric oxide synthase (NOS): neuronal (nNOS), endothelial (eNOS), and inducible (iNOS), synthesize NO from L‐arginine. Moreover, in response to inflammatory stimuli, iNOS can produce copious amounts of NO for prolonged periods that triggers cell death by either necrosis or apoptosis. This has been considered as a key process in demyelination of both CNS and PNS with a destructive and/or protective controversial role. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, which morphology is characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and analysis of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in PNS. With EAN clinical spontaneous recovery, endoneurial iNOS was rapidly down‐regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, whilst necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned normal. These data support the hypothesis that, during cell‐mediated demyelination, iNOS may influence Schwann cell‐axon relationship causing axonal damage and regulating endoneurial cell life and death.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 16
Authors: Basta I , Allaria S , Carpo M , Cavanna B , Nobile‐Orazio E
Published: October 2010

Antibodies to different neural antigens have been reported in patients with dysimmune neuropathies but their pathogenetic role in these diseases is still debated. In order to identify other possible protein target antigens in these diseases we tested by immunoblot IgG and IgM reactivity with human cauda equina and spinal cord in the sera from 30 patients with Guillain‐Barré syndrome (GBS), 14 with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and 11 with multifocal motor neuropathy (MMN). As controls we examined sera from 11 patients with amyotrophic lateral sclerosis (ALS), 68 with other neurological and non‐neurological diseases (OND) and 28 normal subjects. We found high titers (>1/800) of IgG antibodies to some protein bands of the approximate molecular weight (MW) of 45–50 kDa in spinal cord but not cauda equina, in 20 patients (67%) with GBS, and 1 each with MMN and CIDP (9% and 7%, respectively)(GBS vs. MMN/CIDP p < 0.05). In 16 GBS positive patients this reactivity was re‐tested and found reduced during recovery. A similar IgG reactivity with the 45–50 kDa bands was found in 2 patients (18%) with ALS (GBS vs. ALS p < 0.05), 15 (23%) with OND (GBS vs. OND p < 0.001) and in no normal subject. Since the MW of reactive bands corresponded to that of Glial Fibrillar Acidic Protein (GFAP), we tested the serum from 6 intensely positive GBS patients (titers of 1/6400 up to 1/12800) for IgG reactivity with purified GFAP by immunoblot. In four of them IgG bound to GFAP in a pattern similar to that observed with a commercial anti‐GFAP antibody. Pre‐incubation of one of these sera with purified GFAP completely abolished IgG reactivity with GFAP by immunoblot. This study shows that anti‐GFAP IgG antibodies are significantly increased during the acute phase of GBS and decrease during recovery. Further investigation is necessary to clarify their possible pathogenetic role in the disease.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 17
Authors: Scarlato M , Bannerman P , Scherer S , Pleasure D
Published: October 2010

The neuropilins, NP‐1 and NP‐2, are co‐receptors for Sema3A and Sema3F, respectively, both of which are repulsive axonal guidance molecules. NP‐1 and NP‐2 are also co‐receptors for vascular endothelial growth factor (VEGF). The neuropilins and their ligands are known to play prominent roles in axonal pathfinding, fasciculation, and blood vessel formation during peripheral nervous system (PNS) development. To screen for additional molecular mechanisms by which Schwann cells and fibroblasts contribute to successful PNS axonal regeneration, we used cDNA microarrays (Clontech) to compare expression profile of multiple messenger RNAs in sciatic nerves distal to transection with their levels in normal sciatic nerves. An evocative result of this screen was a 14‐fold increase in NP‐2 mRNA in the axotomized nerve segments 4 days post‐transection. We verified that NP‐2 is induced in transected as well as crushed nerve segments by quantitative PCR, Northern blotting, and Western blotting, and examined the distribution of NP‐2 expressing cells in injured sciatic nerves by in situ hybridization. Then, we sought evidences of induction in the injured nerves of the NP‐2 ligands, Sema3F and VEGF, and widened our survey to determine whether expression of the functionally related genes, neuropilin‐1 (NP‐1) and its class 3 semaphorin ligand, Sema3A are also induced in PNS following injury. We showed by in situ hybridization induction of all those genes at four days post‐crushed, distally to the lesion. Our results suggest the possibility that the neuropilins and their semaphorin ligands serve to guide, rather than to impede, regenerating axons in the adult PNS.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 18
Authors: Calaindro P , Padua L , Aprile I , Mondelli M , Pazzaglia C , Foschini M , Tonali P ,   for the “Italian CTS Study Group.”
Published: October 2010

Pregnancy in one of the most frequent physiological conditions associated with CTS. During 2000, the Italian CTS study group (participants: T.Carboni‐San Benedetto del Tronto, S.Massi‐San Giovanni Valdarno; M.Mondelli‐Siena, A.Morini‐Trento, D.Murasecco‐Perugia, L.Padua‐Roma, M.Romano‐Palermo) studied the incidence of CTS in pregnancy in women enrolled in 7 Italian centers. CTS was diagnosed clinically in 62% and neurophysiologically in 43% of women. During 2001, 12 and 15 month follow‐up evaluation was performed. The aims were to evaluate: 1) evolution of CTS after delivery and lactation; 2) predictive value of electrodiagnostic assessment and clinical picture at the time of the first diagnosis. An extensive and complete description of the study design was previously reported. Evolution was assessed on the following CTS severity measurements: SYMPT, FUNCT, PAIN, Hi‐Ob and neurophysiologic class. Overall, at follow up, 20 of 37 women (54%) who presented clinical CTS at first evaluation had clinical CTS. All patient‐oriented measurements showed significant improvement of CTS. Conversely, neurophysiologic findings did not differ between baseline and follow‐up. Although CTS severity measurements improved at follow‐up, more than half of women with CTS symptoms during pregnancy complained of CTS symptoms one year after delivery. Moreover, the onset of symptoms during pregnancy was the most predictive factor for untreated CTS evolution. All patient‐oriented and clinical measurements showed that an earlier onset of symptoms was a negative prognostic factor. According to the neurophysiologic evolution, weight gain appeared predictive: an higher gain implied a lower probability of improvement at follow‐up examination.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 19
Authors: Padua L , Schenone A , Nobile Orazio E ,   for the pilot study NEUROPA group.
Published: October 2010

*Software NEUROPA based on the “consensus” Committee for standardization of measurements on polyneuropathy of the Gruppo di Studio Sistema Nervoso Periferico (Antonimi G, Cavaletti G, Di Iorio G Fabrizi G, Galardi G, Gemignani F, Giannini F, Ghirlanda P, Lori S, Nobile‐Orazio E, Padua L, Scarpini E, Schenone A, Tonali P, Uncini A, Vita G). Kind of study: survey prospective multicentric multidimensional study. Aim of the study: to evaluate the characteristic (including disability and Health Related Quality of life ‐ HRQoL) a representative sample of patients with suspected, or diagnosed, polyneuropathy (or multineuropathy) admitted in neurological centers. The HRQoL dimension of the study was developed with the collaboration of the Quality of Life Study group of the Italian Neurological Society. Timing: The period of enrollment started on 1‐10‐02 e will end on 30‐01‐03. Acquired data: Besides clinical data we acquire data on the diagnostic pathway the patients have done, disability, HRQoL. All the data are monthly sent to the Department of Neuroscience of Università Cattolica where statistical analysis will be performed. Conclusion: The acquired data will provide information on 1) the frequency of the different type of disease we have to study in the different kind of centers; 2) the clinical picture and the actual involvement in daily activity of this kind of patients and therefore the priority we have to give them; 3) the necessities of the neurological centers where this kind of patients are admitted and therefore what we have to requests to the national and regional sanitary service to better study this kind of patients and to optimize the diagnostic and therapeutic pathway. # Antonini G, Bacci A, Cardinali P, Cavalletti G, Cocito D, Corbo, Di Iorio, Fabrizi GM, Fazio R, Galassi G, Gemignani F, Giannini F, Girlanda P, Insola A, Liguori R, Maggio M, Mazzeo A, Messina C, Murasecco D, Nemni R, Nobile Orazio E, Pareyson D, Porazzi D, Quattrini A, Ragno M, Rizzuto N, Romano M, Santoro L, Sartucci F, Sabatelli M, Schenone A, Sghirlanzoni, Siciliano G, Villacara A, Vita G.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 21
Authors: Bianchi R , Savino C , Cavaletti G , Oggioni N , Lauria G , Borgna M , Ghezzi P , Brines M , Cerami A
Published: October 2010

Erythropoietin (EPO) has neurotrophic and neuroprotective effects and its efficacy and safety has been demonstrated in patients with ischemic stroke. We investigated its efficacy in preventing and reversing established nerve disorders in streptozotocin (STZ) diabetes. After STZ injection (60 mg/kg/ip), EPO (5000 units/kg b.w. i.p. three times a week) was started in a group of rats and continued for five weeks (prevention schedule). In another group of diabetic rats, EPO was started six weeks after STZ, continued for five weeks (therapeutic schedule). Groups of non‐diabetic control rats were similarly treated. Antidromic nerve conduction velocity (NCV) in the tail was assessed at five weeks for all groups and at 11 weeks for the therapeutic schedule. Compared to non‐diabetic rats, NCV was 21% lower (P < 0.001) at five weeks in the STZ group, EPO partially prevented this decrease (14% lower than with non‐diabetic controls), with a significant difference from the untreated‐diabetic group (P < 0.01). After six weeks of uncontrolled diabetes, at the beginning of therapeutic EPO, NCV was reduced by 23% and after 11 weeks by 40%, EPO efficacy was confirmed. Thermal (hot plate method) and mechanical (Randall‐Selitto method) nociceptive thresholds were monitored weekly throughout the study. In addition, in all groups, the density of intra‐epidermal nerve fibers, which reflects possible degeneration of somatic unmyelinated fibers, was assessed in the hindpaw using protein‐gene‐product 9.5 immunostaining. Rats developed mechanical hyperalgesia within two weeks after STZ injection. Both the prevention and therapeutic schedules of EPO reduced diabetic hyperalgesia after two weeks of treatment, reaching statistical significance at fur, and five weeks of treatment, with no such effect in non‐diabetic controls. Hindpaw thermal response latencies were significantly (P < 0.001) increased in untreated diabetic rats compared with untreated controls. EPO had no effect on these latencies in control rats but partially prevented the increase in diabetic rats, so the values were still different from controls, but significantly different from untreated diabetics at four and five weeks in both the prevention and therapeutic studies (P < 0.05). These observations extend the therapeutic utility of EPO and highlight its potential for treating established diabetic neuropathies.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 22
Authors: Savino C , Bianchi R , Bernasconi R , Galliani G , Tacconi MTT
Published: October 2010

Experimental diabetic neuropathy has a number of features in common with the human disease, including a reduction of nerve conduction velocity (NCV) and Na+, K+‐ATPase activity in nerve fibers, and alteration of the essential fatty acid metabolism leading to changes in membrane composition. N‐3 polyunsaturated fatty acids (PUFA) are beneficial in different pathological conditions including diabetic complications. Since the PUFA composition of cell membranes largely depends on the diet, most studies have supplemented the diet with fish oil (FO), particularly rich in docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, or DHA and EPA ethyl esters. We have prepared a new formulation of n‐3 PUFA wax esters (WE) enriched in DHA and EPA that have a bioavailability comparable to oil and esters, are easily digestible and are free from most of the previous drawbacks. The present study was designed to measure Na+, K+‐ATPase activity, NCV, and FA content in plasma phospholipids (PL) and to assess the preventive effect of newly formulated n‐3 PUFA‐WE, and individual EPA and DHA‐WE (as compared with standard and FO‐supplemented diets) on these abnormalities. Diabetes was induced by streptozotocin (STZ, 60 mg/kg/ip). After STZ injection, diabetic and non‐diabetic control rats were fed the standard diet (St) without supplementation or supplemented with either FO or n‐3 PUFA‐WE or individual EPA and DHA‐WE, to reach a daily dose of 0.15 g/kg, the experiment continued for five weeks. Analysis of the FA composition of plasma PL, which better reflects FA intake and content in biological membranes, showed that the sums of n‐3 PUFA were double the St diet after n‐3 supplement of independent of the dietary regimen, whereas those of FA of the n‐6 family were not affected by n‐3 supplementation. Thus, the n‐6/n‐3 ratios were reduced from 15:1 with the St diet to 7:1 for the FO and WE diets. Na+, K+‐ATPase activity was significantly lower in diabetic rats (−30–35%), significantly restored in diabetic rats that received FO, n‐3 PUFA and EPA‐WE supplementation, and partially restored by DHA‐WE (9% lower than with non‐diabetic controls). These effects were partially associated with a significant beneficial effect on NCV which was reduced by 20% in diabetic rats. FO protected against this decrease (3%), n‐3 PUFA‐WE were only partially protective (11%), and EPA and DHA‐WE had scant effect. This study indicates that, like FO, n‐3 PUFA‐EPA and DHA‐WE have beneficial effects on diabetic‐induced alterations in sciatic nerve ATPase+‐ATPase activity and, partially, also on NCV. The newly formulated n‐3 PUFA WE offer a potential advantage over products in current use, on account of their greater stability.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 23
Authors: Feltri ML , Saito F , Moore SA , Nodari A , Previtali S , Quattrini A , Messing A , Campbell KP , Wrabetz L
Published: October 2010

Laminin is required for normal peripheral nerve development, as mutations causing absence of laminin‐2 cause hereditary peripheral neuropathies (neuropathy of Merosin‐Deficient Congenital Muscular Dystrophy and dystrophic mouse). We study the laminin receptors, integrins and dystroglycan, that link laminin in the basal lamina to the Schwann cells cytoskeleton. This linkage is defective in an animal model of Charcot‐Marie‐Tooth 4F, in which the Periaxin/Dystrogycan/DRP‐2 complex is disrupted. To study the role of laminin receptors in these peripheral neuropathies, we inactivated the gene for beta1 integrin and dystroglycan specifically in Schwann cells of transgenic mice. alpha6beta1 integrin is present in Schwann cells and their precursors before myelination, the absence of beta1 integrin causes a severe peripheral neuropathy due to the failure of Schwann cells to interact with axons during axonal sorting. Although more severe, this neuropathy is morphologically similar to that of dystrophic mice. In contrast, dystroglycan first appears in Schwann cells after axonal sorting and just prior to myelination (pro‐myelinating Schwann cells). In the absence of dystroglycan, mice develop a neuropathy with abnormally folded myelin sheaths, slow conduction velocity and loss of DRP‐2, similar to that of periaxin‐null mice. These data show that alpha6beta1 integrin and dystroglycan subserve different roles during nerve development, and that they are involved at different steps in the pathogenesis of Merosin‐Deficient Congenital Muscular Dystrophy and Charcot‐Marie‐Tooth 4F.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 25
Authors: Piatti M , Tagliabue E , Tredici G , Marmiroli P , Zoia C , Galbiati S , Rigolio R , Nicolini G , Villa P , Rotondi A , Ferraro R , Resta G , Buda A , Lissoni A , Cundari S , Zanna C , Cavaletti G
Published: October 2010

Several effective antineoplastic drugs are severely neurotoxic and induce the onset of disabling peripheral neuropathies. The clinical presentation of this side effect depends on the type of antineoplastic agent administered. The signs and symptoms shown are predominantly motor (e.g. in the case of vinca alkaloids), sensorimotor (e.g. with the taxanes) or sensory (e.g. using platinum‐derived drugs). The pathogenesis of these antineoplastic drug‐induced peripheral neuropathies is still poorly understood, although a relationship has been suggested between some neuronal growth factors (neurotrophins) and the toxic action of cisplatin (CDDP) and paclitaxel. In this study we correlated the changes in the circulating levels of Nerve Growth factor (NGF) in a series of 24 women affected by locally advanced squamous cervical carcinoma treated with cisplatin and paclitaxel‐based chemotherapy with the severity of chemotherapy‐induced peripheral neuropathy (CIPN) as assessed by the Total Neuropathy Score (TNS). After informed consent, blood samples were drawn before chemotherapy and after treatment and NGF circulating levels were determined by ELISA (EmaxTM ImmunoAssay System, Promega, USA; plasma working dilutions NGF 1:80) following the manufacturer protocols. The results obtained in this series of patients evidenced a significant correlation between the severity of CIPN and the reduction in the circulating levels of NGF (r = − 0.480, p = 0.017 by two‐tailed Spearman correlation test, 95% CL −0.745 to −0.082), thus confirming similar results previously obtained in a rat model of CDDP peripheral neurotoxicity. In conclusion, our data suggest that a relationship exists between CIPN and NGF circulating levels in patients treated with cisplatin and paclitaxel. Therefore, this preliminary observation support the need for further studies in order to explore the possibility of reducing the severity of platinum‐drug sensory neurotoxicity with treatments aimed at increasing the circulating levels of NGF.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 26
Authors: Conti V , Padua L , Caliandro P , Aprile I , Pazzaglia C , Tonali P
Published: October 2010

To our knowledge there are no evidence of other multientrapment neuropathy related to growth hormone (GH) administration. We observed the case of a 45 year‐old bodybuilder complaining of paraesthesias and dysaesthesias in hands and feet after self‐administration of high‐dose of recombinant GH therapy. The patient complained of these transitory symptoms after each cycle of GH therapy. Electrodiagnostic studies showed: 1)“moderate” right CTS and “minimal” left CTS; 2)“mild” right ulnar entrapment at elbow; 3) decrease in left ulnar motor nerve conduction in the segment across the elbow; 4) decrease in left ulnar sensory nerve action potential amplitude; and 5) bilateral absence of ulnar nerve F‐wave from abductor digiti minimi. Our data suggested multiple nerve entrapment at upper limbs. Moreover, basing on the history of feet paraesthesia, we hypothesized a mild involvement of distal sensory fibers in the legs, which was not assessed by neurophysiological studies. The anecdotal history and neurophysiological findings of this case suggest that more attention should be paid to the adverse effects of GH on peripheral nerves.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 27
Authors: Pazzaglia C , Padua L , Mazza S , Aprile I , Caliandro P , Sabatelli M , Tonali P
Published: October 2010

It is well known that exposure to toxic substances may induce peripheral and central neurological complications but no cases of acute cranial nerve involvement are reported after single, although massive, exposure to toxic agents. Cranial multineuropathy is an uncommon occurrence. We observed two atypical cases of multinevritis of cranial nerves with mild sensory symptoms at limbs. Both patients had many common features: acute onset, occurrence of neuropraxic block in cranial nerves, and rapid clinical and neurophysiological recovery after corticosteroid therapy. In both cases, the strict time correlation between substance inhalation and acute onset of symptoms suggested a toxic origin of the disease. We emphasize that multinevritis of cranial nerves could be related to acute exposure of toxic substances. Missing this diagnosis could lead to a delay in treatment.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 33
Authors: Vigo T , Nobbio L , Timmerman V , Van Hummelen P , Abbruzzese M , Mancardi GL , Schenone A
Published: October 2010

CMT1A is a hereditary demyelinating neuropathy due to increased genetic dosage of peripheral myelin protein 22 (PMP22). The functions of PMP22 as a structural protein of peripheral myelin and a regulator of the proliferation, differentiation, shaping and apoptosis of Schwann cells (SCs) are well known. However, the effects of its overexpression on the molecular phenotype of SCs are still unclear. In order to detect genes that are modulated by PMP22 overexpression, we performed a cDNA microarrays experiment on PMP22 overexpressing sciatic nerves from a transgenic model of CMT1A. Differential expression of 117 known genes that are sensitive to PMP22 dosage was observed. The number of up‐ and down‐regulated genes in the transgenic nerves was 99 and 144 respectively, of 22.000 spotted genes. In the up‐regulated group, the number of known genes was 30 and the number of EST was 69. In the down‐regulated group, the number of known genes was 87 and that of EST 57. We classified the differentially expressed genes into functional categories. Among these, we focused our attention on groups of down‐regulated genes coding for cytoskeletal and transmembrane proteins and for extracellular matrix components, like collagens. Moreover we identified a group of genes with chromosomal localization in candidate regions for demyelinating neuropathies. The differential expression of several sequences was confirmed by RT‐PCR, performed both on normal and transgenic rat sciatic nerves, and on primary SCs cultures obtained from normal and CMT1A rats. Therefore, we point out the importance of the interaction between SCs and extracellular matrix and the involvement of SCs cytoskeletal organization in the pathogenesis of CMT1A. Moreover, this study suggests us new candidate genes that could be submitted to sequence analysis in demyelinating CMT.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 38
Authors: Beronio A , Ghiglione E , Reni L , Abbruzzese M
Published: October 2010

Thalidomide has immunomodulatory and antiangiogenic properties. An important dose limiting side‐effect of long term thalidomide treatment is peripheral neuropathy. Thalidomide induces mainly an axonal sensory neuropathy whose incidence is scarcely known. We prospectively evaluated thalidomide‐induced neuropathy using neurological examination and neurophysiological studies. 50 patients with diagnosed Multiple Myeloma were studied. Thalidomide was given at a dosage ranging from 100 to 400 mg/die, orally. Neurological examination and nerve conduction studies (NCS) were evaluated prior and at 3, 6 and 12 months of treatment. Neurological examination included Neurological Symptom Score and Neurological Disability Score. For NCS, amplitude of sensory and motor action potentials (SNAP and MAP) and conduction velocities of median, peroneal and sural nerves, with F wave recording, were evaluated. All patients were asymptomatic at baseline, with a normal neurological examination and NCS. A decline of the SNAP index of 40 % or more (SNAP amplitude at first examination was considered 100 %) was set as the diagnostic marker of axonal neuropathy. Out of 50 patients, 15 discontinued thalidomide for lack of therapeutic response, 15 remained on therapy for 3 months and 20 completed the treatment at 12 months. Incidence of neuropathy, as judged by clinical and neurophysiological criteria, was high (90%) in the group of patients with a 12 months follow up. On the contrary, the incidence of neuropathy in the group of patients with a 3 months follow up and in those treated with a lower dosage, was low (10–20%). In all the patients, who developed a neuropathy, the subjective symptoms preceded NCS abnormalities. Most common symptoms were paresthesias and reduced sensation with a stock and glove distribution. Our data support the view that thalidomide induces very frequently a dose‐dependent axonal neuropathy with only a partial reversibility, and that NCS findings lack of a predictive value.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 40
Authors: Fazio R , Malagutti MC , Sessa M , Previtali S , Amadio S , Quattrini A , Comi GC
Published: October 2010

We describe a 75‐year‐old woman affected by ichthyosis since childhood who developed bilateral lower limb distal muscle weakness resulting in foot deformities and gait disturbances during the last decade. Neurological examination showed equinovarus deformity with pied en griffe, distal motor and sensory impairment and areflexia at lower limbs. On upper limbs mild distal motor impairment and atrophy were present. EMG study revealed an axonal sensory motor polyneuropathy. Sural nerve biopsy showed a severe, predominantly axonal, neuropathy with many clusters of small myelinated fibers and some degree of chronic demyelination with small onion bulbs. Both her sister and the mother have a clinically similar peripheral neuropathy, but in the absence of ichtyosis. Familial history, prevalent motor lower limbs involvement, middle life onset with slow evolution, neurophysiological and neuropathological findings suggest the diagnosis of Charcot‐Marie‐Tooth disease type 2 (CMT 2). Nevertheless, biochemistry and cerebrospinal fluid analysis were performed to rule out known causes of axonal peripheral neuropathy. Ichthyosis has been reported to be associated with some neurological disorders characterized by the presence of peripheral neuropathy such as Krabbe leucodystrophy, Refsum disease, and Rud syndrome. To our knowledge no association has been described between CMT2 and ichthyosis. We believe interesting to point out the presence in our family of CMT2 and ichthyosis. Further studies are ongoing to better elucidate this association.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 42
Authors: Bossi B , Ardolino G , Fabrizi GM , Bertolasi L , Cavallaro T , Polo S , Barbieri S , Rizzuto N , Priori A
Published: October 2010

Connexin 32 (Cx32), a protein involved in gap‐junction formation, in the peripheral nervous system is mainly localized in non‐compact myelin of paranodes and Schmidt‐Lanterman incisures. Despite patients with Cx32 mutations have a polyneuropathic phenotype, the pathophysiological correlates of Cx32 defects on axonal function are unknown in humans. Non‐invasive methods for assessing axonal excitability have been recently developed (Burke et al., Clin. Neurophysiol. 2001, Priori et al. Brain 2002) in humans. These methods allow the indirect estimate of specific ionic conductances of human axons. We assessed the strength‐duration function descriptors, the axonal refractoriness and supernormality in a group of Cx32 defective patients with polyneuropathy. Twenty‐three healthy control subjects (38 nerves) and 5 patients (10 nerves) with a polyneuropathy and a genetic defect of Cx32 were studied. The ulnar nerve was bipolarly stimulated at the wrist and the CMAP was recorded from the abductor digiti minimi muscle. The descriptors (time constant: tsd, rheobasic current: rh50%, threshold: thr100%) of the motor axonal strength‐duration function were estimated according to Priori et al. (2002). Axonal refractoriness was tested by delivering pairs (S1 and S2) of stimuli at variable intervals (10–300 ms). S1 strength was supramaximum, S2 intensity was adjusted to evoke a CMAP 50% of the maximum. The rh50% and the thr100% were markedly increased (rh50% patients [n = 10, mean ± SD] 13 ± 5.7 mA, controls [n = 26] 4.8 ± 2.1 mA, p < 0.0001; thr100% patients 47 ± 24 mA, controls 9.5 ± 3.1 mA, p < 0.0001) in patients. The tsd was abnormal in 70% of patient's nerves Axonal refractoriness was increased in 56% and axonal supernormality was decreased in 56% of patient's nerves. In conclusion, the Cx32 defect induces abnormalities of the strength‐duration function suggesting the involvement of the nodal conductances and axonal hyperpolarization. Hence, the paranodal Cx32 defect functionally spreads to the adjacent nodal region.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 43
Authors: Amadio S , Corradi A , Croci L , Broccoli V , Zecchini S , Previtali S , Wurst W , Maggi R , Del Carro U , Quattrini A , Consalez GG
Published: October 2010

Study aim: the Ebf gene family has been implicated in several developmental processes, ranging from B‐cell development to neuronal differentiation. As the murine Ebf2 gene is expressed in numerous sites of nervous system, Ebf2‐null mice develop hypogonadotropic hypogonadism, due to defective migration of gonadotropin releasing hormone‐synthesizing neurons, and a peripheral neuropathy as well. Therefore, we aimed to study whether electrophysiological tests would be able to detect abnormalities of peripheral nerve function. Methods: 2 groups of mice were studied, which consisted of 8 Ebf2‐/‐ mice and 9 age‐matched controls. The sciatic nerve was stimulated at the ankle and at the ischiatic notch; the compound motor action potential (cMAP) was recorded from the paw muscles with a pair of needle electrodes to measure the motor conduction velocity (MCV). Results: MCV mean values were lower in Ebf2‐/‐(21.8 m/sec; SD 2.9) than in controls (35.2 m/sec; SD 2.6) and the difference was significant (p < 0.001). The mean cMAP amplitude was also decreased in Ebf2‐/‐(6.2 mV; SD 2.7) as compared to controls (9.3 mV; SD 2.6, p < 0.05). Conclusions: electrophysiological tests demonstrated a sharp decrease of sciatic MCV in Ebf2‐/‐ mouse, as consequence of defective axon sorting, segmental dysmyelination and axonal damage revealed by pathological study.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 46
Authors: Padua L , Pareyson D , Quattrone A , Rizzuto N , Vita G , Schenone A
Published: October 2010

Traditional outcome assessment in neurological diseases has always been based on physician‐derived and instrumental findings. Over the last two decades, clinical and public health researchers emphasized the need for a thorough evaluation of concepts such as Health Related Quality of Life (HRQoL) to study the impact of chronic illnesses and their treatments on the patient's life. The most frequent inherited neuropathy is Charcot‐Marie‐Tooth disease (CMT). CMT Patients develop progressive weakness and sensory disturbances, becoming sometimes severely disabled even at very young age. In CMT clinic, neurophysiologic, pathologic and genetic evaluation, are considered fundamental to assess nerve involvement and diagnose, but how these findings are related to HRQoL and disability is not assessed. We propose a prospective follow‐up (24–30 months) of CMT patients with multiple measurements of CMT. Besides conventional clinic, pathologic, neurophysiologic and genetic measurements we adopt validated patient‐oriented measurements to assess HRQoL and disability. Aims of the study are: 1) to assess HRQoL and disability of CMT patients in a wide and well‐represented sample and to evaluate the relationships between conventional parameters and the patient's perception of his own HRQoL and disability; 2) to evaluate natural history of HRQoL and disability in CMT, and to evaluate the predictive value of phenotype, genetic picture, neurophysiological and pathological pattern 3) to develop a national network and a database on CMT disease (this aim includes the standardization, based on a consensus validation process, of the most used terms and measurements in CMT and the development of a database software). In a preliminary reunion, the authors developed a dedicated database for patients affected by CMT. Details about this database will be presented.