bluuebunny/crossref_metadata_2025 huggingface dataset:
Carpal Tunnel Syndrome In Patients With Diabetic Polyneuropathy
Authors: Bril V , Perkins Ba
Published: October 2010

Diagnosis of carpal tunnel syndrome (CTS) in patients with diabetic polyneuropathy (DPN) is important as therapeutic interventions directed towards relief of CTS may be effective irrespective of DPN. The frequency of clinical CTS and the best electrodiagnostic discriminator of CTS from diffuse neuropathy are uncertain. 478 subjects including reference, non‐neuropathic subjects with diabetes mellitus (DM), and diabetic patients with mild, moderate and severe neuropathy were evaluated for clinical features of CTS. All subjects had routine determinations of median nerve distal motor and sensory latencies, sensory and motor potential amplitudes and sensory conduction velocities. Other parameters tested were: ratios of median to ulnar nerve distal motor and sensory latencies, distal motor and sensory amplitudes, and distal conduction velocities. Similar median to sural nerve ratios for sensory latencies, amplitudes and conduction velocities were determined as were ratios of median nerve motor amplitudes and latencies to sural nerve parameters. Segmental median sensory nerve conduction velocities were evaluated. The frequency of clinical CTS was 2% in the reference population, 14% in diabetic patients without DPN, and 30% in those with DPN. We did not find any reliable electrodiagnostic discriminator for CTS in patients with DM +/− DPN. Some of the parameters worsened with severity of neuropathy, but none reliably distinguished diabetic patients with and without CTS. Given that CTS is frequent in patients with DPN, but electrodiagnostic criteria cannot distinguish those with clinical CTS, a trial of therapy may be indicated in these patients regardless of the electrodiagnostic findings.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 4
Authors: Nolano M , Provitera V , Stancanelli A , Saltalamacchia AM , Crisci C , Santoro L
Published: October 2010

A severe sensory neuropathy, mostly involving large myelinated sensory fibers, characterizes Friedreich ataxia since the early onset. Recently, an involvement of unmyelinated nerve fibers has been observed studying cutaneous innervation by means of immunohistochemical techniques and confocal microscopy. Quantification of epidermal nerve fibers (ENFs) by skin biopsy has been extensively used in the last decade to evaluate small‐fiber neuropathies. This minimally invasive procedure, repeatable over time, allows to monitor a neuropathic process. An even less invasive technique is the biopsy of the only epidermis, obtained removing the roof of suction skin blister, sparing basal membrane and vessels. Skin blister, beside a diagnostic tool in sensory neuropathies, is a wound model to study nerve regeneration in human epidermis. The aim of our research was to define the regenerative capability of cutaneous nerve fibers in patients affected by Friedreich's ataxia evaluating time‐course and patterns of nerve fibers regeneration. Six patients (4F, 2M, age 19–34) affected by genetically determined Friedreich ataxia were included in our study. In each subject we induced 5 couples of 2 mm blisters on the forearm. At different time points (1–2–3–4 weeks after blister induction) one blister was removed by 3 mm punch skin biopsy and one was reblistered (3‐mm blister) and the roof removed. The larger size of these biopsies and blisters allowed at including normal skin immediately adjacent to the blister wound. Epidermal nerve fibers were visualised using antibodies to the pan‐neuronal marker protein gene product 9.5 (PGP 9.5) on frozen sections from skin biopsies and on the whole blister roofs. Quantification of ENFs was performed on skin sections using digitised images acquired by confocal microscopy (CARV) and Neurolucida software. Blister allowed to have a panoramic and global view of the regenerative process especially of the collateral extension of axons from adjacent normal epidermis, while biopsy allowed to observe the sprouting from the subepidermal neural plexus. Both these phenomena resulted markedly evident in all FA subjects indicating a normal capability of nerve fibers to regenerate. Blister wound probably induces the release of nerve growth factors stimulating nerve regeneration as in normal subjects. At least for the short period of observation (four weeks) nerve fibers maintained this capability challenging the noxa patogena that leads to their loss.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 8
Authors: Moscato G , Maritato P , Calabrese R , Maestri M , Manfredonia F , Baglini O , Siciliano G , Sartucci F
Published: October 2010

A process of motor units (MU) rearrangement may compensate the loss of motor neurons in spinal cord anterior horns in Amyotrophic Lateral Sclerosis (ALS), at least in the early stages of the disease. Standard electromyography is unable to precisely quantify these pathological changes. Recently, Motor Unit Number Estimation (MUNE) has been introduced in clinical practice in order to provide a quantitative measure of the process as well as short‐ and long‐term follow‐up data. We investigated 8 male patients (mean age ± SD: 64 ± 10.9 yrs, range 45–78) affected by definite or probable ALS according to El Escorial Criteria. In order to quantify the total number of motor units, MUNE was performed during the diagnostic work‐up (basal, T0), after three (T1) and six months (T2), in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. We found a significant decrease in the mean number of motor units (16.6% at T1 [p < 0.002] and 37.9% at T2 [p < 0.04]), recording from ADM, while the decrease in mean and maximal area did not reach the statistical significance at the same time intervals. Similarly, we found a significant decrease in the mean number of motor units (20.6% at T1 [p < 0.008] and 40.3% at T2 [p < 0.0006]), but not in the mean and maximal area, recording from TA. According to previous data, we found about a loss of about 50% motor units in both the muscles six months after diagnosis. We conclude that MUNE is a useful tool to quantify MU loss in ALS and may result helpful in following the course of ALS and in predicting the prognosis.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 12
Authors: Manganaro L , Manente G , Staniscia T , Bertini L , Lanciotti S , Romano F , Uncini A
Published: October 2010

Manente and coll. have recently developed an innovative soft hand brace called Manu for conservative treatment of Carpal Tunnel Syndrome (CTS); a randomised controlled study showed that this hand brace, if worn at night for one month, is highly efficient in relieving symptoms and functional loss in CTS patients. This study aims at evaluating, through Magnetic Resonance Imaging (MRI), the changes of carpal tunnel in CTS patients and controls wearing Manu, the innovative soft hand brace for CTS. Thirteen subjects (9 with CTS and 4 controls) were enrolled in the study. T1 and STIR sequences were performed using a 0.2 T E‐Scan. Some morphologic parameters (tunnel diameters and area, carpus length and nerve signal intensity) were measured at three different scanning levels. Evaluation was carried out before and after the application of the brace. Remarkable differences were recorded in the measurements performed before and after the application of the brace, particularly in the constant increase of front‐rear diameter and tunnel shape rounding. These data could explain the lighter symptoms after using the brace. The Manu hand brace increased the carpal tunnel front‐rear diameter rounding the tunnel shape, hence the clinical efficacy in CTS.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 14
Authors: Toscano A , Mazzeo A , Vita G , Ferlini A , Federico A , Messina C , De Stefano N
Published: October 2010

Transthyretin‐derived familial amyloid polyneuropathy (TTR‐FAP) is the most common form of hereditary amyloidosis, often associated with multisystemic involvement and a poor prognosis. We studied four patients, aged between 43 and 68 yrs, with TTR‐FAP. A severe somatic and autonomic polyneuropathy was seen in three patients, whereas one was at onset of the disease. In addition 2/4, aged 43 and 63 years old, had a mild central nervous system (CNS) involvement. Neurophysiological studies showed an axonal polyneuropathy and amyloid deposits were found in all sural nerve biopsies. Combined conventional MRI and proton MR spectroscopic imaging (MRSI) were performed in our patients and in 14 age‐matched normal controls. Conventional MRI was normal in two patients and showed minimal white matter and subcortical lesions in the other two, who were 63 and 68 years old. Proton MRSI of the periventricular brain regions showed a large reduction in N‐acetylaspartate/creatine (NAA/Cr) resonance intensity (mean NAA/Cr in patients: 2.45 ± 0.04; mean NAA/Cr in normal controls: 2.9 ± 0.1; p < 0.003). Our findings suggest that, despite minimal or no abnormalities on conventional MRI, evidence of diffuse axonal damage can be demonstrated in brain of patients with TTR‐FAP by proton MRSI examination, even in patients with no or mild CNS involvement.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 15
Authors: Dati G , Quattrini A , Dina G , D’Antonio M , Fratta P , Messing A , Feltri ML , Wrabetz L
Published: October 2010

Charcot‐Marie‐Tooth neuropathies and Déjérine‐Sottas Syndrome are associated with mutations in the gene encoding Myelin Protein Zero. Here we report the characterization of two lines of transgenic mice expressing, in addition to the wild type protein, different point mutations in the extracellular domain of P0: the first is a deletion of Ser63 (DSer63), described in Charcot‐Marie‐Tooth 1B patients, whereas the second is a substitution of Ser 63 with a Cys (Ser63Cys) reported in a Déjérine‐Sottas patient. By crossing the transgenic mice with P0 null mice, we produced animals that expressed only the mutated P0. We then investigated in vivo the expression and the effect of the two mutated proteins by morphological, biochemical and immunohistochemical analyses. Sciatic nerves of mice expressing P0DSer63 show severe hypomyelination, with the presence of onion bulbs and some uncompacted myelin sheaths. P0DSer63 does not reach the myelin sheaths and it accumulates in the cytoplasm, where it is probably degraded. In contrast, sciatic nerves of mice expressing P0Ser63Cys present a milder hypomyelination with rare onion bulbs and, surprisingly, normal myelin sheaths. The mutated protein is a full‐length protein that, presumably, is integrated into the myelin sheaths. This study demonstrates that different mutations in P0 glycoprotein, leading to disorders of different severity in human, have different fates in the Schwann cells.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 20
Authors: Vicari LM , Mazza S , Caliandro P , Pazzaglia C , Tonali P , Padua L
Published: October 2010

A 26‐year‐old woman acutely developed bilateral sensory symptoms of carpal tunnel syndrome (CTS). Neurophysiological investigations confirmed the diagnosis of CTS (severe at right and moderate at left hand). Because of the severity of the CTS in young patients without evident causes, we asked some further investigations in order to find a primary disease that might cause CTS. Endocrinological studies revealed a Hashimoto's thyroiditis with hyperthyroidism. She was treated for the thyroiditis with improvement of thyroid function and entrapment syndrome. Neurophysiological controls confirmed the progressive improvement of CTS. The current case suggests to look for subclinical endocrinological disease when severe CTS is found in young patients without mechanical stress condition (work or hobby).
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 24
Authors: Piatti M , Bogliun G , Marzorati L , Tredici G , Villa P , Rotondi A , Ferraro R , Resta G , Fei F , Lissoni A , Cundari S , Zanna C , Cavaletti G
Published: October 2010

The present study was performed with the aim to compare different clinically‐based neurotoxicity scales with a more extended composite scale (Total Neuropathy Scale) already validated in diabetic patients, in order to improve the grading of chemotherapy‐induced peripheral neuropathy (CIPN) severity. The features of CIPN were evaluated in a series of women affected by locally advanced squamous cervical carcinoma treated with cisplatin and paclitaxel– based chemotherapy by clinical examination, neurophysiology and quantitative sensory testing of vibration threshold (VDT); the ECOG, Ajani and NCIC‐CTC grades were assessed by a neurologist after clinical examination and the TNS was calculated after additional instrumental examination. At the same time, the treating oncologist, who was blinded as regards the results of the neurological examination, assessed the NCIC‐CTC sensory neurotoxicity grade. The correlation existing between the different evaluations was evaluated with the Spearman test on a total of 97 visits. Our results indicate for all the neurotoxicity scales commonly used by oncologists and evaluated in this study a significant correlation with TNS; the interexaminer agreement comparison evaluation evidenced that in several cases the neurologist attributed a higher grade in the NCIC‐CTC scale than the oncologist, and this discrepancy was mainly due to a different evaluation of the sensory impairment. In conclusion, the TNS can be used to assess effectively the severity of CIPN and the results of this evaluation can be reliably correlated with the oncological grading of sensory peripheral neurotoxicity; the wider range of TNS values, however, can allow a more accurate grading of the sensory impairment, a feature which can improve the estimate of CIPN changes, particularly in clinical trials; finally, the use of standardized methods of examination of the sensory function (e.g. the semiquantitative measure of vibration sensibility using the 128 Hz tuning fork) may reduce the interexaminer disagreement.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 28
Authors: Cimini N , Ferracci F , Macrì E , Cavallaro T , Moretto G
Published: October 2010

A 60 y.o. female was investigated for progressive distal paresthesias, which had started a few years before. Neurological examination revealed mild sensory ataxia, areflexia in lower limbs with normal motor function. Routine laboratory tests were unremarkable; autoantibodies to non‐organ‐specific, extractable nuclear and cytoplasmic antigens were absent and CSF was normal; neurophysiologic findings showed absent sural sensory responses. Sural nerve biopsy revealed a complete depletion of large and small myelinated fibers without aspects of regeneration; no vascular or perivascular inflammation nor changes suggestive of vasculitis were detected. Salivary gland biopsy showed focal lymphocytic infiltrates. Late systemic manifestations included dry skin, xerophtalmia and arthralgias. Severe sensory neuropathy is rarely associated with Sjögren syndrome. It occurs more frequently in female patients and its major pathologic process is believed to be a dorsal root ganglionitis.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 29
Authors: Cimini N , Ferracci F , Mondardini V , Squintani G , Moretto G
Published: October 2010

Tick‐born encephalitis (TBE) is caused by a Flavivirus infection after Ixodes Ricinus bite. Among the 62 cases of TBE virus infection observed in the Belluno General Hospital since January 1994, 4 patients (6,6%) presented also signs of lower motor neuron involvement. One patient exhibited severe tetraplegia with respiratory failure. The clinical picture was monomelic in the remaining 3 patients. In all patients reflexes were absent in the affected limbs; sensations were preserved. Needle EMG revealed signs of acute denervation, prominent in proximal muscles. Motor and sensory conduction velocities were within normal limits. The outcome was good in the three patients with monoparesis who recovered normal muscle strength. The tetraplegic patient is still wheel‐chair bound. Polio‐like syndromes due to TBE virus infection have been described either in anecdotal reports or in small series of patients from continental Europe. The pathophysiology of the motor neuron damage is unknown.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 30
Authors: Benedetti L , Grandis M , Nobbio L , Mancardi GL , Caponnetto C , Primavera A , Beronio A , Ghiglione E , Manzino M , Schenone A
Published: October 2010

Mycophenolate mofetil (MM) is a new generation immunosuppressant, which has been successfully used for treatment of renal, heart and liver transplants, and other immune‐mediated diseases. MM is also a safe and steroid‐sparing agent for treating neuromuscular diseases, like chronic inflammatory demyelinating neuropathy and myastenia gravis. MM is an ester of mycophenolic acid, an agent that inhibits the proliferation of B and T lymphocytes. Side effects are modest and there is a lower risk for late malignancies than other immunosuppressive drugs. We assessed MM in the treatment of multifocal motor neuropathy (MMN). The therapy of MMN largely depends upon the use of intravenous immunoglobulins (IVIg). IVIg induce and maintain improvement in MMN, but they do not eradicate the disease and are very expensive. No randomized controlled trials are available to indicate whether immunosuppressive agents are beneficial in MMN. We treated with MM four patients who fulfilled the clinical, laboratory and electrodiagnostic criteria for MMN, aiming to assess whether the drug is safe and may help in reducing or discontinuing IVIg infusion in this disease. MM administration, at 1 g twice daily, was started when patients were still under IVIg treatment and showed minimal or no disability, as judged by the INCAT disability scale. At the third month of MM therapy, IVIg infusion was discontinued in 2 patients and reduced by 20 % in 2 patients. After a follow up ranging from 1 to 6 months, no worsening in the INCAT disability scale was observed in all the patients. One patient discontinued the medication after four months because of gastrointestinal discomfort with diarrhea, weight loss and increased amylase/lipase levels. The promising response to MM and the lack of major side effects, warrant further multicentric controlled trials in MMN.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 31
Authors: Quattrini A , Biffi A , Previtali S , Dina G , Bordignon C , Naldini L
Published: October 2010

Autologous hematopoietic stem cells (HSC) have been transferred with third generation lentiviral vectors, expressing the green fluorescent protein (GFP), under the human PGK promoter, and transplanted in wild type mice. Transplanted mice have been sacrificed at 6, and 9 months after bone marrow transplantation (BMT) to study the timing and extent of migration of BM derived transduced cells into peripheral nervous system (PNS). Starting from 6 months after BMT cells have been found in the PNS, such as in the acoustic ganglion, the dorsal root ganglions (DRG) and the sciatic nerve. At 9 months from transplant GFP positive cells represented the 50–60% of the F4/80 (a microglial marker) positive population of sciatic nerve sections and the 65–75% of F4/80 + cells of the acoustic ganglion and DRG. At these sites, GFP positive cells were found between nerve fibers and neurons, they expressed F4/80, and were negative for GFAP, neuronal and myelin markers. Autologous BMT coupled with HSC transduction with high efficiency vectors could provide therapeutic benefit to several disorders affecting the PNS such as many lysosomal storage disorders. In these patients clinical evidence confirms the relevance of PNS involvement in the prognosis of the disease.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 34
Authors: Previtali SC , Zerega B , Dina G , Dalcin E , Mustafa AMS , King RHM , Feltri ML , Wrabetz L , Quattrini A , Bolino A
Published: October 2010

CMT4B1 is an autosomal recessive peripheral neuropathy characterized by severe progressive muscular atrophy with childhood onset, decreased conduction velocities, demyelination with myelin outfolding, and subsequently axonal loss. The disease gene has been recently identified as myotubularin‐related 2 (MTMR2), encoding a protein phosphatase (Bolino et al., Nature Genetics 25: 17–19; 2000). Although this phosphatase is widely expressed, the disorder is restricted to the peripheral nervous system, just as mutations to the related and broadly expressed phosphatase MTM1 produce only myotubular myopathy. The function of MTMR2 and the pathogenetic mechanism of CMT4B are still unknown. We produced several new polyclonal antibodies to MTMR2 in order to better dissect the expression and potential function of MTMR2 in the peripheral nervous system. Although CMT4B manifests primarily as demyelinating neuropathy, our expression data show that MTMR2 protein is present in both Schwann cells and axons in peripheral nerve. In Schwann cells, MTMR2 is localized in the cytoplasm and, at lower level, in the nucleus, while no major differences were observed between non‐myelin forming and myelin‐forming Schwann cells. DRG sensory neurons and motor neurons, as well as their axons, show MTMR2 expression in their cytoplasm. Thus, it remains unclear whether demyelination in CMT4B is the consequence of a cell‐autonomous or a cell‐extrinsic defect, the latter possibly due to a defective interaction between Schwann cells and axons.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 35
Authors: Mazzeo A , Nastasi V , Autunno M , Musolino C , Majorana G , Girlanda P , Vita G , Messina C
Published: October 2010

A 41‐year‐old man suffered for 1 year of severe progressive sensorimotor polyneuropathy that rendered him bedridden in few months. Routine laboratory investigations, including serum protein immunoelectrophoresis and immunofixation, were normal. Electrophysiological studies and sural nerve biopsy showed a severe mixed axonal and demyelinating polyneuropathy. X‐ray showed multiple osteosclerotic lesions in the spine. MRI disclosed pachymeningeal thickening of the brain and meningeal infiltration at cauda equina level with gadolinium enhancement. Bone marrow biopsy revealed 12% of plasma cells with a monotypic immunocytochemical profile for lambda light chain. A diagnosis of osteosclerotic myeloma (OM) was done. He received two courses of IVIg followed by melphalan and prednisone without any benefit. Very recently he underwent a bone marrow autotransplantation. OM is a rare variant of multiple myeloma, representing less than 3% of all myeloma cases. In contrast to multiple myeloma, in OM half of patients have a peripheral neuropathy similar to CIDP, with or without features of POEMS syndrome. MRI meningeal involvement, concomitant with a severe neuropathy, was not yet described in OM. A paraneoplastic process in addition to a direct neoplastic infiltration may account for the severity of the disease in our patient, despite different therapeutic approaches.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 36
Authors: Logullo F , Manicone M , Sabbatini D , Di Bella P
Published: October 2010

Diabetic lumbosacral radiculoplexus neuropathy (DLRPN) is a well‐recognized subacute painful asymmetric proximal and distal lower limb neuropathy. DLRPN may be associated with thoracic and upper limb involvement. The latter may appear as compression mononeuropathies and as a more diffuse disorder consistent with cervicobrachial radiculoplexus neuropathy (DCRPN). We performed a multiperspective study of patients, seen between 1999–2002, with diabetes and acute or subacute onset and progression of unilateral or asymmetric bilateral proximal and/or distal weakness in lower and/or upper limbs. We excluded patients who had compression mononeuropathies or radiculopathies, multineuropathies or asymmetric poly(radiculo)neuropathies, motor neuron disease as suggested by clinical, electrophysiological, laboratory or MRI findings. During the study period we observed 18 patients with diabetic radiculoplexus neuropathy. Most patients were middle‐aged or elderly and male preponderance was noted. Ten patients had DLPRN, 6 both DLPRN and DCRPN, 2 isolated DCRPN. DCRPN affected prevalently hands and forearms, unilaterally in 3 patients, bilaterally in 5, and improved spontaneously but incompletely in most patients in several months. Pain was not a prominent feature except for one patient. We conclude that diabetic radiculoplexus neuropathy may involve the cervicobrachial regions not only in association with DLRPN but also alone.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 39
Authors: Malagutti MC , Quattrini A , Munerati E , Del Carro U , Fazio R
Published: October 2010

A 40‐year‐old smoker complained of pain, deep and burning in character, constant, and persistent, associated with paresthesias in his feet for a period of two years. Furthermore, he developed aching non‐traumatic foot ulcers. There was no history of diabetes and systemic illness. Neurological examination revealed loss of all modalities of sensation and hyperhidrosis in the limbs with a prominent distal‐to‐proximal gradient. The following laboratory tests were normal: blood count; test for liver, kidney, and thyroid function; cryoglobulins; anti‐HCV antibodies and HIV. Neurophysiological investigation revealed an axonal neuropathy with a distal‐to‐proximal distribution in the limbs. Sural nerve biopsy showed a severe chronic axonal neuropathy. Prominent thickening of endoneurial microvessel endothelial cells was present with narrowing of lumen. Congo Red staining was negative. He initiated treatment with alprostadil alfa‐ciclodestrina and stopped smoking. The patient reported prompt improvement of neurologic symptoms as well as skin abnormalities few months after the begin of therapy. Ischemic neuropathy in which nerve damage occurs in the more distal portion of the limbs has been reported. In our patient, clinical presentation, neurophysiological and neuropathological findings suggest the diagnosis of a Lower Extremity Ischemic Neuropathy probably triggered by smoke.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 41
Authors: Laurà M , Aguennouz M , Mazzeo A , Santoro M , Catania MA , Calapai G , Vita G
Published: October 2010

Nuclear factor kappa B (NF‐kB) is an ubiquitous transcription factor expressed in a wide variety of cells and involved in immune and inflammatory responses. Many recent data suggest his important role in human inflammatory neuropathies. The present study investigated expression and activation of NF‐kB in experimental autoimmune neuritis (EAN), a clinical and histopathological model of acute inflammatory demyelinating polyneuropathy. EAN was induced in 11 Lewis rats by injection of peripheral bovine myelin. 4 animals, two immunized with complete Freund's adjuvant and two normal, were used as controls. The clinical course was assessed. Immunohistochemistry, western blot of nuclear extract proteins and electrophoretic mobility shift assay (EMSA) were performed in the sciatic nerves removed at different times of the disease. Immunoreactivity for the activated form p65 of NF‐kB was found in the endoneurial vessel walls, in the external myelin of some nerve fibers and at level of some endoneurial infiltrating cells 14 and 21 days after immunization. No immunoreactivity was found after 7 days as well as in controls. A single band corresponding to NF‐kB p65 was detected in all animals, except for the normal controls. EMSA analysis showed a complex binding band in all EAN rats, which was stronger in peak and recovery phase of disease. Our results strongly suggest a crucial role of NF‐kB in the genesis of inflammatory demyelination in the peripheral nervous system occurring in EAN.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 44
Authors: Madia F , Sabatelli M , Quaranta L , Lippi G , Conte A , Mereu ML , Tonali P
Published: October 2010

50–60% of CIDP patients show a clinical remission with the administration of standard therapies. Unfortunately, the achievement of this goal does not conclude patients’ troubles but coincide with the beginning of another story whose course is often uncertain. In our study of CIDP patients we attempted to establish the fate of 36 patients showing an initial remission after treatments. Over a long‐term period of follow‐up, we observed that the disease in these patients can follow 3 different clinical courses. A first group of 11 patients had a monophasic disease. All of them achieved a complete remission after therapy with corticosteroids and no relapses were observed after drug interruption over a follow‐up period of 6 months‐12 years. The duration of treatment varied between 3–24 months. A second group of 6 patients had a relapsing course; these patients became asymptomatic with corticosteroids but relapsed after a period of time of at least six months (range 6 months‐16 years) since therapy suspension. The number of relapses varied from 1 to 4. A third group was represented by patients (19 in our series) who needed continuous treatment over a long period of time to maintain improvement. The apparent relapsing‐remitting course in these patients was always related to tapering of therapies. The duration of this chronic active form ranged from 2 to 17 years. 5 patients of the last group were able to top therapies without evidence of worsening over a follow‐up period of 2–12 years. This subgroup of patients had a prolonged monophasic course rather than a relapsing‐remitting form. Our findings show that CIDP is a heterogeneous disease encompassing cases with a single monophasic episode in which the term “chronic”, with respect to GBS, is referred mainly to the prolonged phase of worsening and cases in which the chronic nature of the condition in outlined by the long duration (up to decades) of the “active phase”, made‐up of therapy‐related relapses/remissions.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 45
Authors: Quaranta L , Sabatelli M , Madia F , Lippi G , Conte A , Mereu ML , Tonali P
Published: October 2010

Unclassified neuropathies still represent a challenge for neurologists, since in about 20–30% of patients no cause can be identified after extensive investigations. In this context, some patients sharing peculiar features have been reported as to be grouped in a single entity termed Chronic Idiopathic Axonal Polyneuropathy (CIAP). The onset occurs in middle to late adulthood, there is a predominant sensory involvement and progression is slow, usually not disabling. Electrophysiologic and pathological studies are consistent with a primary axonal injury. We describe five patients affected by adult‐onset chronic “idiopathic” axonal neuropathy with an unusual course characterized by severe disability. Onset occurred in the fifth‐seventh decades with sensorimotor symptoms and signs involving both lower and upper limbs with a distal distribution. Over a 2–14 year follow‐up, the disease showed a progressive course with severe muscle weakness and atrophy of semi‐distal and distal muscles in all patients, and involvement of proximal muscles in four of them. Two patients died because of respiratory and heart failure. All five patients were sporadic. Extensive laboratory examination excluded identifiable causes of neuropathy. Nerve biopsy was carried out in all patients and showed an axonal neuropathy. Amyloid deposits were not observed in nerve sections nor in abdominal fat aspirate. In four patients, treatment with steroids and IVIg was unsuccessful. The nosology of acquired adult‐onset axonal polyneuropathies is difficult to be drawn, since in most cases the etiology remains obscure. Our findings suggest that, in this not yet well defined group of neuropathies, different subtypes may exist and represent distinct entities.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 47
Authors: Ragno M , Capasso M , Caporale CM , De Angelis MV , Lupo S , Di Muzio A , Uncini A
Published: October 2010

A 38‐year‐old man begun to have paresthesias in the last three fingers of the left hand followed in few months by paresthesias in the right hand, weakness of distal muscles in upper limbs and paresthesias of lower limbs. HCV positivity was discovered by routine blood test. Neurological examination, 18 months after onset, showed asymmetric weakness and sensory loss with a nerve distribution more on the right side. Electrophysiological examination showed a sensory‐motor demyelinating neuropathy with motor conduction blocks and or excessive temporal dispersion of proximal compound muscle action potential in five nerves. Coexistence of focal motor and sensory conduction blocks at the same sites was demonstrated in three nerves. CSF examination showed increased protein content (66 mg/dl) and no cells. Cryoglobulins were absent. Active HCV‐RNA replication was detected in the serum by RT‐PCR. Liver biopsy revealed chronic hepatitis. Sural nerve biopsy showed fiber loss, prevalently of large diameter fibers, asymmetrical between fascicles and few clusters of regeneration. There were no demyelinating features, onion bulbs or inflammatory infiltrates. Weakness and electrophysiological findings worsened after high doses intravenous immunoglobulins but improved after intravenous methylprednisolone and interferon alpha treatment with resolution of conduction blocks in two months. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), as in the patient we describe, is a rare disorder considered an asymmetric variant of chronic inflammatory demyelinating neuropathy (CIDP). HCV infection is usually associated with a multineuropathy due to vasculitis or a symmetric sensory‐motor axonal polyneuropathy. CIDP has been described but never MADSAM. It is difficult to be sure of a pathogenetic link between a dysimmune demyelinating neuropathy and HCV infection, nonetheless the coexistence of hepatitis makes the choice of treatment problematic in these patients.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 48
Authors: Santoro L , Manganelli F , Lanzillo R , Pierelli F , Barbieri F , Santorelli F
Published: October 2010

We describe two first cousins presenting a CMT phenotype associated with progressive external ophthalmoplegia (PEO) in one of them. The propositus (ML), a 37‐year‐old man, showed a severe muscular involvement both proximal and distal, bilateral ptosis, external ophthalmoplegia, hypophonia, bilateral pes cavus and absence of deep tendon reflexes (DTR). The cousin (MC), a 27‐year‐old man, showed a CMT phenotype with marked peroneal atrophy, pes cavus and absence of DTR. Cranial nerves were normal. Electrophysiological study revealed in the propositus, a severe axonal and demyelinating neuropathy and clear myopathic features at EMG. Accordingly, muscle biopsy showed both signs of mitochondrial myopathy and chronic denervation. Furthermore, nerve biopsy confirmed the severe axonal loss and showed abnormalities of myelin sheath which was thinner in relation to the axon diameter. In MC the electrophysiological study and the muscle and nerve biopsies showed only signs of a marked axonal neuropathy. Genetic analysis showed in the propositus a new homozygous mutation in POLG gene that encodes the mitochondrial DNA polymerase gamma. The same mutation was present in the heterozygous state in his parents and in MC. Moreover, the recent observation that mutations in GDAP1 gene could be associated with both axonal and demyelinating autosomal recessive CMT, prompted us to search for point mutations in this gene. However, the direct sequencing of GDAP1 gene did not show any mutation. In conclusion we describe two cousins presumably affected by an axonal autosomal recessive CMT. The presence in the propositus of the homozygous mutation of polymerase gamma gene adds to the CMT phenotype the myopathic features and PEO. It is questionable if in ML the axon hypomyelination could depend on the POLG gene mutation.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 49
Authors: Capasso M , Angiari C , De Angelis MV , Caporale CM , Di Muzio A , Fabrizi GM , Rizzuto N , Uncini A
Published: October 2010

A 65‐year‐old woman was referred because of bilateral foot drop, pes cavus and distal muscular atrophy. Electrophysiological studies showed prolonged distal motor latencies and conduction velocities ranging from 33 to 42 m/s in upper limb nerves. A conduction block (P/D area = 0.4) was present in the wrist elbow segment of median nerve. Her 42‐year‐old daughter was asymptomatic and neurological examination revealed only absent deep tendon reflex. The 35‐year‐old son complained of positional paresthesias and had normal examination. The 13‐year‐old nephew was completely normal. There was no history of pressure palsies. All three proband's relatives showed: 1) normal or slightly slowed motor conduction velocities; 2) slowing of conductions in the above‐below elbow segment of both ulnar nerves (difference of velocity with the below elbow‐wrist segment ranging from 16 to 25 m/s). Sural nerve biopsy in the proband showed at light microscopy a chronic demyelinating and remyelinating process. On teased‐fiber examination virtually all fibers showed myelin thickenings or classical tomacula. Molecular analysis showed neither deletion of the 17p11.2 segment nor mutation of the PMP 22 gene. The sequence of MPZ/PO revealed a 306delA at codon 102 in the proband and three relatives. The mutation was of non‐sense type and causes a frameshift with a premature stop codon (Val102fs). Motor conduction velocities in CMT1B are usually < 20 m/s although a predominantly axonal variant with intermediate range conduction velocities has been also reported. Focally folded myelin has been reported in a few CMT1B patients usually, as in our cases, harboring a mutation in the extracellular domain of P0. In conclusion this CMT1B family is electrophysiologically peculiar because of the coexistence of intermediate‐normal motor conduction velocities with segmental slowing and conduction block. Focal conduction abnormalities may be pathophysiologically related to tomacula at the paranodal region.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 52
Authors: Bonetti B , De Toni L , Marconi S , Battistini L , Borsellino G , Nardelli E
Published: October 2010

Gangliosides (Gs) have been implicated as potential antigens in autoimmune neuropathies and anti‐tumoral immune response, but their role in paraneoplastic neuropathy has been poorly investigated. We describe one patient affected by lung adenocarcinoma and subacute motor axonal neuropathy with high titres of IgG1 and IgG3 to several Gs. Expansion (3% of total T cells) of peripheral g/d T lymphocytes was found, as compared to healthy controls (<0.5%) and to patients with lung neoplasia without neuropathy (1.1%). At three months after neoplasia removal, we observed stabilization of the neuropathy, decline of anti‐Gs IgG and of g/d T cells, which dropped to normal values. Expression of GM1, GD1a, GM2 and GM3 was found by immunohistochemistry on patient's neoplastic cells, but not in control lung neoplasia. Absorption experiments of anti‐Gs IgG revealed that only GD1a and GM1, among all Gs tested, significantly decreased anti‐Gs IgG reactivity. Indirect immunohistochemistry with biotinylated IgG purified from the patient showed positive signals on motoneurons, dorsal root ganglia, axonal structures and Schwann cells and his own neoplastic cells. At autopsy, IgG deposits were found on the same neural targets. Purified IgG from the patient exerted high levels of cytotoxicity on both Schwann and neuroblastoma cells, as compared to healthy controls. The association of neoplasia, peripheral neuropathy and autoimmune responses to Gs observed in our patient proposes a pathogenetic role for Gs as putative autoantigens in paraneoplastic neuropathy.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 56
Authors: Cocito D , Ciaramitaro P , Isoardo G , Barbero P , Pipieri A , Poglio F , Durelli L
Published: October 2010

OBJECTIVE: Interferon is regarded as a promising treatment option for patients with chronic inflammatory demyelinating polyneuropathy. However, sporadic cases of axonal PNP and one case of CIDP after treatment with Interferon (INF) alfa‐2a were reported. The objective of this study was to test the onset of PNP in patients affected by relapsing‐remitting MS after treatment with INF beta‐1b. METHODS: from the OPTIMS trial we have selected 23 patients (9 males, 14 females; mean age 30.5; range 22–50) with diagnosis of relapsing‐remitting SM in treatment with INF beta‐1b (8–12.000.000 UI). In these patients bilateral motor nerve conduction study (NCS) of peroneal, tibial, median, ulnar nerves and antidromic sensory NCS of sural, median and ulnar nerves were performed according standard techniques. All patients (23/23) were submitted to neurophysiological tests before the treatment (T0), 16/23 (7 drop out) after six months (T1) and after nine months of therapy (T2). RESULTS: at T0 no patient showed electrophysiological signs indicating PNP; after six and nine months of therapy (T1 and T2) no patient submitted to NCS showed alterations in the PNS either. CONCLUSIONS: all tested patients showed absence of electrophysiological signs of PNP as side effects after one year of treatment with high dose of INF beta‐1b.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 60
Authors: Ariatti A , Galassi G , Nichelli PF , Barbieri A
Published: October 2010

Brachial amyotrophic diplegia (BAD) is defined the isolated upper limb weakness attributed to neurogenic atrophy, sparing lower extremity, respiratory and bulbar muscles. Although such phenotypes may be seen in number of conditions, previous reports pointed out that the label of BAD should refer to any patient with slowly and nonprogressive neurogenic atrophy of upper limbs remaining stable at least 18 months after initial presentation 50 year old man with unremarkable past history noticed after minor cervical spine trauma progressive weakness and wasting of left shoulder and arm which was followed within few months by gradual involvement of contralateral in relatively symmetric pattern. There were no symptoms in lower limbs, neck, bulbar muscles nor sphincter disturbances. On examination, patient exhibited a peculiar posture of both hands hanging loosely at his sides. There were fasciculations and atrophy of upper limb muscles. Reflexes could not be elicited in upper extremities but they were normal in the lower. Cranial nerves and sensory examination were unremarkable. Routine blood tests and search for GM1 antibodies were negative, whereas CK was found mildly elevated ( 361 mU/ml). Test for HIV‐1 was positive with RNA level of 144.920 copies/ml and CD4 count 403/mm3. Electrophysiology showed in both sides low amplitude of compound muscle action potentials, mildly reduced velocity without evidence of conduction block or of temporal dispersion. Sensory conduction study was normal. On EMG, there was loss of motor units, acute and chronic neurogenic changes. Cervical MRI was normal. Patient neurological disability did not show progression. The case reported exhibits the following notable aspects: clinical and electrophysiological abnormalities fully restricted to upper limbs, lack of significant demyelinating features as well as of GM1 antibodies, absence of clinical signs related to immunosuppression due to HIV‐1 infection.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 63
Authors: Cardinali P , Serrao M , De Dominicis L , Pucci E , Forconesi F , Parisi L , Rossi P , Amabile G
Published: October 2010

We report a case of a 50‐ year‐old patient, diagnosed as having mycosis fungoides since 1 year, was admitted to our Hospital for progressive weakness and sensory loss in upper and lower limbs. On neurological examination, moderate weakness of the distal muscles of upper and lower limbs, ataxia, loss of proprioceptive and tactile sensation of the hands and foot and diffuse areflexia were noticed. The electrophysiological evaluation revealed signs of prevalent axonal sensory‐motor polyradiculoneuropathy and the cerebrospinal fluid showed a marked increase of proteins and a mild increase of cells. A biopsy of the sural nerve revealed a severe axonal loss with preservation of myelin. The possible pathogenetic mechanism of this extremely rare peripheral neuropathy and the differences from previous reports are discussed.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 64
Authors: Bellone E , Di Maria E , Balestra P , Cassandrini D , Ribizzi G , Schenone A , Ajmar F , Mandich P
Published: October 2010

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant, demyelinating peripheral neuropathy. HNPP is a genetically homogeneous disease with a single disease locus at chromosome 17p11.2‐p12. The major cause of HNPP is a 1.5 Mb deletion containing the PMP22 gene, which causes a dosage effect of peripheral myelin protein 22. The deletion is found in 85% of patients with HNPP. A few HNPP patients show smaller deletions, still containing the PMP22 gene. Point mutations in the PMP22 gene are rare cause of HNPP. To date, nine point mutations were reported and all these mutations most likely cause a loss of function of PMP22. We describe a HNPP patient who at the age of 20 years developed muscle weakness and paresthesias. The neurophysiological examination showed a sensory motor demyelinating polyneuropathy at four limbs. The sural nerve biopsy showed signs of a demyelinating neuropathy with abundance of classical tomacula and mild inflammatory reaction in endo‐ and epineurial tissues. The CMT1A duplication and HNPP deletion of the region 17p11.2 was excluded by Southern blot analysis and pulse field gel electrophoresis. The PMP22 gene was screened for mutations by single strand conformation polymorphism (SSCP) analysis. An altered SSCP fragment was observed in the exon 2. Direct sequencing demonstrated a nucleotide substitution in the exon 2‐intron 2 junction (c.179 + 1G?C). To define the molecular consequences of this splice site mutation, RT‐PCR experiments on the sural nerve biopsy are in progress. The pathophysiological role of this mutation will be discussed in the light of the clinical, neurophysiological and pathological features.

Partially supported by grants MURST 2000 to F.A. and Ministero della Sanità to P.M.