bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 51
Authors: Porfiri L , Capriotti T , Zamponi N , Tavoni MA , Cardinali C
Published: October 2010

We report a case of peripheral both demyelinating and axonal polyneuropathy in a patient affected from intestinal aganglionosis with high dose intermittent metronidazole therapy. Intestinal aganglionosis is a myenteric plexus disorder with lack of innervation concerning the whole digestive tract from the rectum to the esophagus. The familial incidence of this condition seems to be high and a recessive autosomal transmission is likely. In the pathogenesis of this disorder aberrant neural crest migration seems to be implicated: indeed frequent neurologic signs resembling dysautonomic ones, deafness and rare peripheral demyelinating or axonal neuropathies are associated. The patient was a 12 years old female child affected by intestinal aganglionosis and underwent to chronic intermittent Metronidazole treatment, with daily doses of 500 mg for 15 day every month. She was admitted to our Hospital for inability to walk, dysesthesias and pain at lower limbs, acutely started and progressively worsening. At the admission neurological examination showed ataxic gait with bilateral foot drop, severe distal weakness, bilateral tibialis anterior muscle atrophy, absent deep tendon reflexes, rapidly worsening. CSF was normal. Antibodies against to peripheral nerve (antigangliosides, sulfatide, MAG, glycosaminoglycans) resulted negative. Spinal cord MRI revealed increased roots size and increased epidural space. EMG showed denervation spontaneous activity with neurogenic MUAP modification on distal muscles. Nerve conduction study showed severe slowing of motor velocity on right and left peroneal nerves with reduced amplitude of CMAP. Sensory conduction was mild slowing on both sural nerves with reduced amplitude of SAP. Metronidazole therapy was discontinued; desametazone, high dose vitamin and intravenous immunoglobulin therapy was established in addition to rehydration and parenteral nutrition. Clinical conditions progressively improved and at two months follow up the girl was able to walk with mild ataxia. The authors emphasize in described case the difficulty to differentiate toxic or vitamin deficiency or autoimmune pathogenesis.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 53
Authors: Del Corona A , D’Avino C , Cafforio G , Falorni M , Moretti P , Abbruzzese A , Solito B , Pistolesi S , Fontanini G , Siciliano G
Published: October 2010

Inclusion body myopathy (IBM) is a myopathy causing asymmetric proximal and distal limb muscle involvement in patients over 50 years. Motor neuron disease (MND) is a neurodegenerative disorder involving upper and lower motor neuron in the spinal cord and brainstem, characterized by progressive muscle weakness resulting in paralysis. The pathogenesis of cell injury in both diseases is still unknown: several hypothesis have been proposed addressing viral, autoimmunity, genetic and oxidation stress factors. We report on 2 cases with clinical presentation of upper and/or lower motor neuron involvement and histopathological diagnosis of IBM. Case 1: a 68 years old man with an 18‐month history of progressive weakness, spasticity, dysarthria, dysphagia. Neurological examination showed generalized muscle weakness, wasting of the finger flexors and quadriceps, fasciculations, deep tendon hyperreflexia. Electromyography (EMG) showed neurogenic signs and fasciculations at limbs and tongue muscles. Nerve conduction studies showed reduced cMAP amplitude at the legs, Motor Evoked Potential (MEP) revealed marked pyramidal tract involvement. Blood examination showed increased E.S.R. with normal level of serum creatinine kinase, copper, ceruloplasmin, and iron. Antiganglioside antibodies titer was normal and blood lactate analysis showed normal values during exercise. Cerebrospinal fluid (CSF) examination showed increased protein level. Brain magnetic resonance imaging disclosed of involvement of the cortico‐spinal tract and deposits of paramagnetic material in the basal ganglia with normal dopaminergic receptorial SPECT binding. Muscle biopsy revealed a neurogenic myopathy with “rimmed vacuoles”. Case 2: a 64 years old woman with 20 month history of muscle weakness slowly progressing from upper to lower limbs. Neurological examination showed distal muscle weakness and wasting at the upper limbs, deep tendon hypo‐areflexia. EMG showed neurogenic signs and fasciculations at four limbs. MEP and nerve conduction studies were normal but H reflex and F late responses were absent. E.S.R. was increased, while antiganglioside antibodies titer, thyroid hormones dosage and CSF examination were normal. Muscle biopsy revealed a neurogenic myopathy with rare “rimmed vacuoles”. These case reports, although not nosologically defined, confirm the clinical variability of the IBM and rise questions on the possible mechanisms of neuronal damage in motor neuron syndromes.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 54
Authors: D’Avino C , Cafforio G , Del Corona A , Galluzzi F , Siciliano G
Published: October 2010

Guillain‐Barré syndrome (GBS) is the prototype of post‐infectious autoimmune neurological disease. Campylobacter Jejuni is the most frequent pathogen antecedent causing a clinical picture characterized by severe, pure motor axonal involvement with IgG antibodies against GM1, GM1b, GD1a or GalNAc‐GD1a gangliosides. As for viral infection, CMV is the most common antecedent associated with demyelinating sensory GBS and anti‐GM2 IgM antibody. Miller‐Fisher syndrome (MFS) is a GBS variant characterized by ataxia, areflexia and ophthalmoplegia associated with anti‐GQ1b IgG antibody. We describe the case of a 41 year‐old man who developed muscle weakness with gait disturbance, paresthesiae and pain at four limbs, taste and voice disturbances 9 days after cutaneous eruption by varicella zoster virus (VZV) infection. At hospital admission the clinical evaluation showed ataxia, deep tendon areflexia, hyposthenia at lower limbs, hypophonia and dysgeusia. Examination of the cerebral spinal fluid (CSF) showed a slight increase in protein concentration with no concomitant pleocytosis; nerve conduction velocity detected the absence of H reflex. At present antibodies titration against gangliosides is under examination. He underwent plasma exchange treatment and is still receiving acyclovir therapy with clinical recovery. Conclusion: this case underlines the clinical variability of acute polyradiculoneuropathy presenting after viral infections other than those classical described with possible overlapping to GB and MF syndrome and confirms the good response to combined gammaglobulin and acyclovir therapy.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 57
Authors: Cocito D , Chiò A , Isoardo G , Ciaramitaro P , Ghiglione P , Poglio F , Vercellino M , Mutani R , Bergamasco B
Published: October 2010

BACKGROUND: Since 1991, five sets of electrophysiological criteria for CIDP have been reported. However, until now, receiver operator characteristic (ROC), such as sensitivity and specificity, of only AAN criteria were investigated, showing a high specificity, but intermediate sensitivity. The application of these criteria may be useful in clinical trials, but is inadequate in clinical practice, since they preclude immunomodulating treatment in patients who do not meet them. OBJECTIVE: 1) to evaluate the ROC and predictive value of five different electrophysiological criteria for CIDP (AAN, INCAT, Rotta et al, Nicholas et al. and Saperstein et al.); 2) to identify the most informative electrophysiological features indicative of demyelination by mean of the likelihood ratio; 3) to determine, in our series of cases, a set of minimal electrophysiological criteria (albeit aspecific) enough sensitive for CIDP diagnosis. PATIENTS AND METHODS: 20 patients with sensorimotor polyneuropathy, progressive for at least 2 months, with weakness in least two limbs and documented improvement in strength in response to immunotherapy. Other potential causes were excluded, including diabetes and IgM paraproteinemia with or without anti‐MAG reactivity. Twelve patients with axonal polyneuropathy associated with diabetes and 12 patients with amyotrophic lateral sclerosis were included as controls. Nerve conduction studies (NCS) were evaluated according to all five sets of NCS criteria and ROC was calculated. Likelihood ratio for CIDP was evaluated for each set of NCS criteria and for presence of each of the following features in different number of nerves: motor conduction velocities (MCV), conduction blocks/temporal dispersion, distal motor (DML) and F‐wave latencies (FWL). MCV, DML and FWL were considered indicative of demyelination if decreased or increased as suggested by AAN criteria. Results will be discussed.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 58
Authors: Leone M , Galassi G , Barbieri A
Published: October 2010

GBS is characterized by ascending motor paresis, hypo/areflexia, minimal objective sensory symptoms, electrophysiological evidence of demyelination, CSF albuminocytologic dissociation. Several related syndromes are regarded as variants being the pathogenesis considered an autoimmune attack on peripheral nerve antigens. A 42‐year‐old veterinary was admitted because of severe myalgias following one‐day high fever. Twelve hours later, he experienced dysphonia, dysphagia, and difficulty in chewing. Clinical examination showed: normal eye movements, bilateral facial weakness, tongue paralysis, limb and trunk sensory ataxia. Muscle strength was minimally affected and deep jerks were weakened. Sensory testing revealed distal loss for pin‐prick, vibration, and position sense in the four extremities. Normal laboratory included emato‐urinary tests, CK, rheumatology and endocrine profiles, microbiological and viral screenings. Search for enteric Campylobacter jejuni was negative. CSF protein was 160 mg/dl (normal < 45). In serum, antiGQ1b IgG were elevated. On admission, electrophysiology was normal. Twenty days later, in motor nerves conduction velocity was normal whereas evidence of demyelination was limited to prolonged F‐waves and terminal latencies. IVIG (0.4 g/kg/daily for five days) produced transient improvement. Because of relapse of sensory symptoms, 10 days later a course of PE was performed with benefit. Patient was followed clinically during six months showing almost complete recovery. In conclusion, we report an acute neuropathy with benign course, high protein in CSF, predominant involvement of sensory fibers, electrodiagnostic evidence of demyelination. The nosologic position of this case seems to fit the criteria of GBS sensory variant. The detection in serum of antiGQ1b IgG proposes similarities with FS and with ataxic GBS suggesting a continuity and a possible common autoimmune mechanism attacking either Schwann cells or motor axons.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 61
Authors: Galassi G , Suozzi R , Tassone G
Published: October 2010

We describe a patient affected by MMN with CB exhibiting unusual progression and clinical features. MMN is a chronic immune mediated demyelinating neuropathy characterized by slowly progressive painless asymmetrical weakness usually in distal limb muscles. GM1 antibodies are found in high titer in 22%‐ 84% of cases. Electrophysiological findings are CB not at usual sites of compression, abnormal temporal dispersion and F‐waves, normal or near‐normal sensory conduction studies. This 63 year old woman was referred for evaluation of one year and half duration weakness which began in right upper limb and progressed to contralateral and to lower extremities. On first admission (July 2001) neurological examination showed normal cranial nerves and sensory testing, severe asymmetric weakness mainly proximal in the upper extremities and distal in the lower. There were atrophy of small hand muscles and weak deep reflexes. She denied sensory symptoms. There were no upper motor neuron signs. Laboratory tests including CK, tumor marker, CSF, anti‐GM1 antibodies were unremarkable. Electrophysiological study was consistent with MMN with CB. Patient underwent IVIG (0.4 g/kg/daily for five days) and PE without significant improvement. In October 2002, her conditions rapidly worsened: she became quadriplegic, unable to swallow, to chew and to protrude her tongue. Admitted to ICU because of respiratory failure, tracheotomy was performed. Repeated searches for GM1 antibodies gave negative results. CSF was still normal. IVIG was administered twice with partial benefit although severe disability persisted. The case presented has notable features: the rapid monophasic progression to quadriplegia within two years and half, the acute worsening in absence of precipitating events and of systemic illness, the severe involvement of cranial nerves and respiratory muscles. The late response to IVIG is in favor of an immune mediated disorder despite the absence of GM1 antibodies.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 62
Authors: Briani C , Zara G , Della Libera S , Rondinone R , Doria A
Published: October 2010

Thalidomide seems to be effective in the treatment of cutaneous forms of lupus erythematosus refractory to other therapies. Peripheral neuropathy is the most severe side effect, but the incidence of neuropathy and its relation to thalidomide doses are still unclear. We prospectively monitored 12 patients treated with thalidomide for cutaneous lupus erythematosus in order to estimate the occurrence of side effects, particularly peripheral neuropathy. A total of 12 female patients, median age 38,6 years (range 26–56), with subacute or chronic cutaneous lupus erythematosus were considered. The patients were treated with low dose thalidomide (starting dose 100 mg, tapered to 50 mg/day or 50 mg alternative day) for up to 18 months. The average follow‐up period was 8,6 months (range 2–18). Prior to, and regularly during treatment patients underwent neurological evaluation and electrophysiological study of at least 8 nerves in the 4 arms (ulnar, median, sural, peroneal nerves). At recruitment, one patient presented a sensory‐motor peripheral neuropathy. Of the remaining 11 patients, six did not present electrophysiological evidence of neuropathy, one had a carpal tunnel syndrome and four showed slowing of ulnar nerve velocity at elbow. No patients developed neuropathy neither worsening of electrophysiological parameters during thalidomide treatment. The most common side effect was tremor, always reversible after withdrawing or reducing thalidomide. Paresthesias, somnolence, amenhorrea, constipation were also present. Only one patient had to stop the therapy for the occurrence, 10 days after taking 50 mg of thalidomide, of a severe, stabbing, “zoster‐like” thoracic pain, which disappeared upon withdrawal of the drug. Started again on thalidomide, the symptoms reappeared and the patient definitely interrupted the therapy with benefit. All the 11 patients who continued on the therapy presented a significant improvement or remission of the cutaneous alterations. These preliminary data seem to indicate that low dose thalidomide is efficacious and tolerable for cutaneous lupus erythematosus. Peripheral neuropathy seems not to be a major side effect. A longer follow‐up and the study of more patients are needed to confirm the results.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 65
Authors: Bellone E , Di Maria E , Gulli R , Balestra P , Cassandrini D , Bado M , Doria L , Schenone A , Ajmar F , Mandich P
Published: October 2010

Mutations in a gene encoding a novel protein of unknown function, the ganglioside‐induced differentiation‐associated protein 1 gene (GDAP1), are associated with one of the autosomal recessive forms of Charcot‐Marie‐Tooth disease (CMT4A). Mutations in GDAP1 can cause both axonal and demyelinating inherited peripheral neuropathies. The GDAP1 gene maps on chromosome 8q21.1, encompassing 13.9 kb of genomic DNA. The coding sequence is comprised of six exons. Little is known about the function of GDAP1. The mouse homologue Gdap1 is highly expressed in brain. Northern‐blot analysis showed that GDAP1 is also expressed in peripheral nerves, both in neurons and in Schwann cells. A series of Italian patients with demyelinating (n = 42) and axonal (n = 39) peripheral neuropathy with possible recessive inheritance was screened for mutations in the GDAP1 gene. The entire coding region, including exon‐intron boundaries, was examined by single strand conformation polymorphism (SSCP) and direct sequencing. All patients were negative for the 17p11.2 duplication and for mutations in the MPZ, GJB1, PMP22 and EGR2 genes. SSCP analysis showed a few electrophoretic variants, in the exon 1, exon 3 and exon 4, respectively. Direct sequencing demonstrated the presence of a common single nucleotide polymorphism in the exon 4 (c.507T > G) and a nucleotide substitution in the exon 3. The latter was found in four patients, belonging to three families, and was not detected in a series of normal subjects. Further studies are in progress to evaluate the possible role of this variant in the pathophysiology of the disease. This work was partially supported by grants MURST 2000 to F.A. and Ministero della Sanità to P.M.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 67
Authors: Giannini F , Volpi N , Bibbò G , Rossi S , Greco G , Magi S , Alessandrini C
Published: October 2010

Sporadic inclusion body myositis (IBM) is a late onset idiopathic inflammatory myopathy, characterized by rimmed vacuoles and cytoplasmic or nuclear tubulofilamentous inclusions. Clinical features are proximal and/or distal weakness, frequent muscle atrophy, hyporeflexia and poor responsiveness to steroid treatment. The involvement of peripheral nerve in both sporadic and familial IBM is a debated issue. Among six cases (five men; age range: 65–82 yrs.) of muscle biopsy proven sporadic IBM, we found variable neuropathic changes. Myogenic/neurogenic mixed EMG pattern was detected in four patients. Sensory and motor nerve conduction studies showed abnormalities consistent with axonal multiple mononeuropathy in three and with axonal polyneuropathy in two patients, whereas one subject had no neurogenic findings. However, the degree of peripheral nerve impairment was usually mild and not related to severity of myopathy. Sural nerve biopsy was performed in the case with more prominent clinical and electrophysiological polyneuropathy. Moderate homogeneous loss of myelinated fibers, with recurrent regeneration clusters and atrophic/degenerating axons were observed. No segmental demyelination was present. In spite of marked inflammatory changes in muscle, neither mononuclear cell infiltrates nor filamentous inclusions were detected in nerve. Similarly, whereas paracrystalline mitochondrial inclusions were observed in muscle, minor but recurrent mitochondrial changes were detected in nerve. Muscle mitochondrial abnormalities have been reported about twice in IBM compared with other inflammatory myopathies. A relation of this finding with high incidence of associated peripheral neuropathy in IBM and mitochondrial myopathies has been hypothesized. On the other hand, the follow‐up of our patients shows improvement of nerve conduction values in clinically responders to intravenous immunoglobulin treatment, suggesting a significant role of immune processes for the pathogenesis of nerve damage in IBM.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 69
Authors: Massa R , Palumbo C , Cavallaro T , Panico MB , Di Muzio A , Bei R , Terracciano C , Rizzuto N , Bernardi G , Modesti A
Published: October 2010

Demyelination and Schwann cell (SC) proliferation are hallmarks of hypertrophic demyelinating neuropathies, of which Charcot‐Marie‐Tooth type 1 A (CMT1A) neuropathy is the typical example. In CMT1A, an altered dosage of the PMP22 gene determines a defect of myelination and an abnormal SC phenotype, characterized by hyperplasia and abnormal differentiation. The Epidermal Growth Factor (EGF) family of proteins, including EGF and neuregulins, and their receptors, namely EGFr and the erbB family, control growth and development of SC. Their expression in mature SC is down‐regulated but, during Wallerian degeneration or chemical myelinolysis, these receptors are transiently over‐expressed, suggesting a potential autocrine mechanism. On the other hand, neuregulin 1 inhibits SC myelination and induces demyelination and SC dedifferentiation and proliferation. These effects might play a role in the pathogenesis of hypertrophic demyelinating neuropathies. We have therefore immunolocalized EGF, EGFr and the erbB receptors (erbB 2, 3 and 4) in sural nerve biopsies from patients with CMT1A as compared to chronic inflammatory demyelinating neuropathy (CIDP) nerve biopsies and to normal nerves, in order to evaluate if the expression of these molecules is up‐ or down‐regulated in these disorders. Among CMT1A nerves, immunoreactivity for EGF, EGFr, erbB2 and erbB3 was moderately to markedly increased in SC, particularly in onion bulbs, in most cases, while a mild to moderate expression of erbB 4 in SC cytoplasm was observed in a few cases. On the other hand in CIDP, which shares with CMT1A histopathological features such as de‐remyelination and SC hyperplasia, only the expression of erbB 3 was up‐regulated in a minority of cases. Since in SC the functional neuregulin receptor is a heterodimer, composed by erbB2 and erbB3, the parallel up‐regulation of these two molecules in CMT1A may bear a functional significance. This would be confirmed if an overexpression of neuregulins could be demonstrated, along with our finding of an increased expression of EGF and its receptor. In conclusion, it can be hypothesized that, in CMT1A, a persistent activation of neuregulin signaling pathways not only is indicative of SC dedifferentiation but also may contribute to demyelination and onion bulb formation or maintenance.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 70
Authors: Lauria G , Borgna M , Morbin M , Lombardi R , Sghirlanzoni A , Pareyson D
Published: October 2010

The availability of antibodies against the pan‐axonal marker protein‐gene‐protein 9.5 (PGP) allowed to definitely demonstrate the existence of small‐diameter nerve fibers within the vital layers of the epidermis and prompted to their quantification in sensory neuropathies. However, morphological features of intra‐epidermal nerve fibers (IENF) have not been fully characterized. We performed immunohistochemical and confocal immunofluorescence studies in skin biopsies taken in 15 healthy subjects at the proximal thigh or the distal leg using anti‐PGP, anti‐unique b‐tubulin (TuJ1), anti‐non‐phosphorylated microtubule‐associated protein‐1B (MAP‐1B), anti‐70 and 200 kDa neurofilament (NF), anti‐phosphorylated neurofilament‐312 (SMI), anti‐peripheral myelin protein‐22 (PMP22), anti‐basic myelin protein (MBP), and anti‐myelin associated glycoprotein (MAG) antibodies. IENF density was quantified under light microscope using PGP, TuJ1, MAP‐1B, NF, and SMI immunostaining. In each site, the density of TuJ1‐ and MAP‐1B‐positive IENF was similar to that of PGP‐positive IENF, whereas that of NF‐positive IENF was significantly lower. Only sporadic SMI‐positive IENF were found. Double confocal staining studies confirmed that TuJ1 and MAP‐1B diffusely co‐localized with PGP in IENF. These findings suggest that IENF cytoskeleton is predominantly composed by tubules, whereas neurofilaments are less represented. No IENF showed PMP22, MBP, or MAG labeling. All dermal nerve fibers presented PMP22 immunoreactivity, which labeled Schwann cell membrane, whereas only a few of them were MBP‐ or MAG‐positive, confirming that most fibers are unmyelinated. Double staining confocal microscope studies revealed that PMP22 labeling in dermal nerves stopped at the dermal‐epidermal junction, whereas TuJ1‐positive axons crossed it and run between keratinocytes. This definitely demonstrates that IENF are naked axons, arising from sub‐papillary unmyelinated nerves which loose the Schwann cell at the dermal‐epidermal junction. The presence of naked nerve fibers within the epidermis suggests that functional interactions with the resident cells, even in sensory transduction, might exist.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 74
Authors: Lettieri C , Inglese C , Preda P , Alfieri S , Gemignani F , Marbini A
Published: October 2010

It is well known that painful neuropathy of the small fiber type is frequent in Fabry disease, however it has been rarely investigated in childhood. We report an 11‐year‐old boy without known familial history of neuromuscular diseases, who complained of painful symptoms in the lower extremities by age 9. Initially pain was present only in association with fever, but during the last year it was triggered also by mild variations in the environmental temperature, so that the boy, to prevent pain, was forced to stay barefooted for most the time during spring and summer, and to wear at least two or three pairs of socks during winter. Physical and neurological examination was negative, except for several small red spots in the testes. Neurophysiological study was negative, but EMG showed motor unit potentials with possible myopathic pattern. Muscle biopsy was unremarkable, apart from endothelial cells containing electron dense lipid inclusions of regular lamellar structure, which were seen also in skin biopsy within fibroblasts, pericytes and endothelial cells. Intraepidermal nerve fiber density was within normal limits (5.5/mm at distal leg and 8.3/mm at proximal thigh), but prominent axonal swellings (possible predegenerative changes) were frequently seen. Diagnosis of Fabry disease was confirmed by deficiency of alfa‐galactosidase. Symptomatic treatment with gabapentin was started, in addition to enzyme replacement therapy. Symptoms of small fiber neuropathy in Fabry disease may be present in early disease as an onset manifestation, and the occurrence of small fiber neuropathy during childhood strongly suggests a diagnosis of Fabry disease. Painful symptoms may occur before a significant intraepidermal nerve fiber loss is seen, and are probably correlated to predegenerative changes in the small sensory fibers.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 75
Authors: Lombardi R , Erne B , Pareyson D , Morbin M , Lauria G , Steck AJ , Schaeren‐Wiemers N
Published: October 2010

Monoclonal IgM antibodies against myelin‐associated glycoprotein (MAG) are associated with a chronic demyelinating neuropathy characterized by predominant involvement of large sensory fibers, although nerve conduction study reveals preferential demyelination of distal motor fibers. In sural nerve biopsy, deposits of monoclonal IgM are found at sites of MAG localization such as Schmidt‐Lanterman incisures and paranodal loops, but also on the surface of myelinated nerve fibers (mesaxon). Distal involvement in sensory fibers cannot be assessed by routine studies. Therefore, we investigated sensory fibers by skin biopsy in 13 patients with anti‐MAG neuropathy. Patients with CIDP (n = 8) and with IgM anti‐MAG negative paraproteinemic neuropathy (n = 3) were used as diseased controls. Skin biopsy was performed using a 3 mm punch at the proximal thigh (n = 20), at the distal leg (n = 21), at the hand or arm or fingertip (n = 23). Specimens were processed to quantify the density of intra‐epidermal nerve fibers (IENF) using the anti‐protein gene product 9.5 (PGP 9.5). Both anti‐MAG patients and CIDP patients showed a proximal‐distal gradient in IENF density decrease, indicating a length‐dependent fiber loss, as typically seen in other neuropathies. Further, we investigated anti‐MAG immunoreactivity and the presence of IgM deposits in dermal myelinated fibers by confocal microscopy. IgM deposits were detected on the surface of MAG positive fibers in the dermis of 11 anti‐MAG patients (85%), but not in diseased controls. IgM deposits were also located at paranodal loops. Our study shows that small myelinated fibers in the skin are involved in anti‐MAG neuropathy, and that IgM deposits can be demonstrated in terminal sensory fibers. Skin biopsy provides a useful, minimally traumatic method for early diagnosis as well as for follow‐up studies of anti‐MAG neuropathy. Supported by a Fellowship of the European Neurological Society.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 79
Authors: Del Carro U , Fiorina P , Fazio R , Amadio S , Malaguti MC , Colleluori A , Mazzolari G , Urban I , Lauria G , Previtali S , Quattrini A , Secchi A , Comi G
Published: October 2010

Peripheral neuropathy is one of the most common secondary complications of diabetes mellitus, causing severe and prolonged morbidity. However, clinical and experimental studies have reported that careful glucose control may prevent, stabilize, and/or reverse neuropathy and other chronic diabetic complications. Unfortunately, insulin therapy does not prevent the development or progression of chronic lesions in the vessels, kidneys, eyes, or nerves of the diabetic patient. There is great interest in investigating other forms of endocrine replacement therapy, such as transplantation of the pancreas or of the islets of Langerhans (IT). Diabetic polyneuropathy (DP) evolution is characterized by progressive demyelination and axonal loss and is manifested by signs and symptoms on physical examination and abnormalities in nerve conduction studies (NCS). NCS provide reliable, noninvasive, objective measures of peripheral nerve function and constitute the most important technique for the evaluation of the severity of DP in clinical trials. Several research groups have demonstrated that skin biopsy with measurement of intraepidermal nerve fiber density is another method minimally invasive and repeatable that provides direct pathologic evidence of axonal damage in diabetic neuropathy. Fifty‐one consecutive IDDM patients with or without end stage renal disease were enrolled at the moment of islet (Is), kidney (KD), kidney‐pancreas (KP) or kidney‐islet (KI) transplantation. Patients underwent skin biopsy punch, neurologic examination and neurophysiological investigation. Particularly, 20 pts underwent KP tx, 16 KD tx, 10 islet tx and 5 KI. The patients were comparable for duration of diabetes, dialysis (when present), age, lipid profile. In half of the patients a follow‐up of 2 years has been reached. After KP tx, and partially with KI, a complete normalization of glycometabolic control has been achieved, with statistically lower HbA1c in comparison with KD group (KP = 6.2; 0.1% vs. KD = 8.4; 0.5%; p < 0.01). In the KI/Is group, a long‐term restoration of islet endocrine function has been achieved, with insulin independence. When this has been lost, a persistent secretion of C‐peptide was shown for a long period of time. This was correlated with a global improvement quality of life and vascular structure. Preliminary results will be presented.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 81
Authors: Lori S , Fasulo A , Reali MF , Nistri R , Toni S , Bardini MR , Zammarchi E
Published: October 2010

Symptomatic neuropathy in young patients with type 1 Diabetes Mellitus (t1DM) is rare but subclinical peripheral alterations can be assessed by electroclinical evaluation. This study aimed to assess prevalence of clinical and subclinical peripheral neuropathy in patients with t1DM. Motor and/or sensory nerve conduction studies of both median, ulnar, peroneal, tibial and sural nerves and standard clinical examination of peripheral nervous system were performed in 83 patients (27 females and 56 males) with diabetes onset since five years. The mean age of patients was 19.89 (range 9–28.3) years, the mean disease duration was 9.61(range 4.4–19.3) and the mean age at the onset of diabetes was 9.02 (range 0.8–23.5). Five patients (6.02 %) had both symptomatic (light clinical abnormalities as paresthesias and mild reduction of vibratory sensibility) and electrophysiologic neuropathy and six (7.2 %) with mild abnormal nerve conduction studies were totally asymptomatic (subclinical neuropathy). The majority of symptoms and electrophysiological alterations were found on the lower limbs. Only two patients had a minimal distal neuropathy of median nerve. No patients showed laboratory evidence of early renal complications or systemic hypertension; 5 (6.02 %) had early diabetic retinal abnormalities as microaneurisms, seen by fundus examination. Analysis of sex, age of onset, duration of diabetes, age at the date of electrophysiologic examination, Hemoglobin A1c (mean level of the last two years), association with retinal abnormalities and clinical assessment was performed (Fisher Exact Test, ANOVA). No correlation was found with the age at the onset, retinal abnormalities and glycaemic control index. Peripheral neuropathy was significantly related with patient age at the date of electrophysiological study and duration of t1DM.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 86
Authors: Milani M , Cesani M , Baratta S , Caccia C , Pareyson D , Taroni F
Published: October 2010

At least 15 genetic loci and ten genes have been associated with the demyelinating form of Charcot‐Marie‐Tooth hereditary neuropathy and related disorders. As pathogenic mutations have been identified in more and more genes, the labor and expense of screening for such mutations has increased substantially. Using conventional methods such as direct sequencing, single‐strand conformation polymorphism (SSCP), or heteroduplex analysis, molecular diagnosis of CMT remains laborious due to the large number of exons to be screened. Some genes (MPZ, PMP22, EGR2, GJB1) are small and have to be analyzed in a relatively large number of patients while other rarer genes, such as periaxin (PRX, 19q13), are too large (7 exons encoding transcripts of 4.8–5.5 kilobases) to be easily included in a molecular diagnostic panel. Furthermore, the sensitivity of the more economical techniques (SSCP and heteroduplex analysis) is far from being optimal ( ). Denaturing High‐Performance Liquid Chromatography (DHPLC) is a newly developed method to scan DNA for mutations, which is capable of automated high‐throughput analysis that does not require modified PCR primers, specific reagent arrays or detection labels, or any sample pretreatment other than PCR. We have undertaken the mutational analysis of some genes associated with CMT1 and related neuropathies by using DHPLC. Optimal conditions have been determined for DHPLC analysis of MPZ, PMP22, GJB1 and PRX genes in an initial group of 30 patients with severe demyelinating neuropathy, negative for the common 17p11 duplication. The very high sensitivity of the method was demonstrated by analyzing a control group of patients with known mutations in the MPZ, PMP22 and GJB1 genes. The work is still in progress. Thus far, DHPLC has resolved all the mutations previously detected by sequencing and allowed the identification of a number of polymorphic variants in the PRX gene and a novel disease mutation in MPZ gene exon 4 in a patient with an intermediate (axonal‐demyelinating) form of CMT. Interestingly, this mutation had consistently appeared as homozygous at previous direct sequencing analysis. DHPLC clearly showed the heterozygous state of the mutation, thus demonstrating the power of this technique also in identifying sequencing artifact or mutation mosaicism, if any. Partially supported by a grant Ricerca Finalizzata Ministero della Sanità to FT.
Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 87
Authors: Jann S
Published: October 2010

Inflammatory vasculopathy is observed in 20 to 66% of nerve biopsies in diabetic neuropathy, especially in patients with proximal diabetic neuropathy (diabetic amyotrophy) or with other patterns of multifocal neuropathy. Moreover there is growing evidence that diabetic patients have an increased predisposition to Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Many authors suggest that there is a more pervasive contribution of inflammatory and immuno‐mediated damage to the pathogenesis of diabetic neuropathy than had previously been imagined. In these patients, immunosuppressive therapy is indicated. However differentiating CIDP in diabetic patients from diabetic neuropathy (DNP) may be difficult. We tried to differentiate immuno‐mediated and inflammatory neuropathies in diabetic patients with polyneuropathy revealing the presence of matrix metalloproteinases (MMPs) in the endoneurium. MMPs are calcium‐dependent zinc endopeptidases which are able to degrade the basement membrane and thus contribute to tissue destruction and cell invasion. Sural nerve biopsies were taken from 10 diabetic patients with CIDP and 5 patients with DNP. Immunohistochemistry was performed for T‐cells, macrophages, von Willebrand factor and MMP‐9. Endoneurial and epineurial immunoreactivity was evaluated and quantified separately. Small epineurial T‐cells infiltrates were present in 5 out of 10 CIDP patients and in none of DNP patients. In CIDP patients 53% of endoneurial vessels were immunoreactive for MMP‐9 against only 12% in DNP patients and this difference reached a statistical significance. In conclusion we demonstrated that immunoreactivity of MMP‐9 is strongly enhanced in diabetic patients with CIDP but not in patients with DNP. The pattern of immunoreactivity may help to select patients for a trial with immunosuppressant drugs.
Paraplegia associated with brucellosis involving the anterior lumbrosacral nerve roots
Authors: Hidir Ulas Umit , Hamamcioglu Kemal , Eroglu Erdal , Odabasi Zeki , Alanoglu Ece , Demirkaya Seref , Gorenek Levent , Vural Okay
Published: October 2010

Abstract We report the case of a 21‐year‐old man with paraplegia due to brucellosis involvement of lumbosacral anterior roots. Lumbosacral magnetic resonance imaging showed contrast enhancement of anterior roots and the anterior part of duramater. Conduction block was found at the level of the lumbosacral anterior roots by electrophysiological studies, including magnetic stimulation study. Wright agglutination, Rose Bengal tests and bacterial culture obtained from cerebrospinal fluid confirmed the diagnosis of neurobrucellosis. Oral administration of ceftriaxon with additional rifampin was effective, and after 3 months of treatment, laboratory data resolved and clinical signs partially improved.
Severe chronic sensory‐motor polyneuropathy: coexistence of 3 unrelated etiologies in a type 1 diabetic patient. A case report and review of the literature
Authors: Micco Andrea , Nobile‐Orazio Eduardo , Baron Pierluigi , Conti Giancarlo , Napoli Laura , Serafini Massimo , Scarlato Guglielmo , Scarpini Elio
Published: October 2010

Abstract We present the case of a 58‐year‐old man, who has suffered from type 1 diabetes mellitus since he was young. He had monoclonal IgM kappa gammopathy of undetermined significance and high anti‐MAG antibody titer. He developed a polyneuropathic picture with the clinical and laboratory features of chronic inflammatory demyelinating polyneuropathy within the span of approximately 2 years. He benefited from IV administration of high doses of immunoglobulins. Investigation of all parameters, but particularly of the clinical phenotype, can lead to a better definition of the polyneuropathic picture, especially for therapeutic and prognostic purposes.
Distribution of perfluoroalkyl compounds and mercury in fish liver from high-mountain lakes in France originating from atmospheric deposition
Authors: Ahrens Lutz , Marusczak Nicolas , Rubarth Janne , Dommergue Aurélien , Nedjai Rachid , Ferrari Christophe , Ebinghaus Ralf
Published: October 2010

Environmental context.Perfluoroalkyl compounds and mercury are of rising concern because of their persistency, bioaccumulation potential and possibly adverse effects on humans and wildlife. In the present study, perfluoroalkyl compounds and mercury were quantified in fish liver from high-mountain lakes in which the contamination originated from atmospheric deposition. This study improves our understanding of atmospheric transport and deposition of these contaminants.
Abstract.Perfluoroalkyl compounds (PFCs) and total mercury (THg) were investigated in fish liver collected from four high-mountain lakes in the French alps in which the water was fed only by atmospheric deposition. Concentrations of various PFCs, including C9–C15 perfluoroalkyl carboxylates (PFCAs) and perfluorooctane sulfonate (PFOS) were quantified. The PFOS concentration was similar in all high-mountain lakes with mean concentrations ranging from 3.61–4.24 ng g–1 wet weight (ww) indicating homogeneous atmospheric deposition. Conversely, the spatial distribution of PFCAs and THg was strongly influenced from a different emission source, which is probably the city of Grenoble, which resulted in significantly higher concentration levels of ∑PFCAs in three lakes (P < 0.001) and of THg in two lakes (P < 0.05) located easterly from Grenoble. Furthermore, the positive correlation between PFCAs and THg suggest similar transport and bioaccumulation pathways. The contribution of the longer chain PFCAs decreased with increasing distance from the local source area of Grenoble, which could be attributed to their less pronounced transport potential. Results from this study demonstrate that the contamination of PFCs and THg in the fish of the high-mountain lakes originated from atmospheric deposition and subsequent bioaccumulation.
Ecosystem functioning from a geomicrobiological perspective – a conceptual framework for biogeochemical iron cycling
Authors: Schmidt Caroline , Behrens Sebastian , Kappler Andreas
Published: October 2010

Environmental context.Microbial ecosystems are characterised by the interplay of various microorganisms with their biotic and abiotic environment. Biogeochemical niches host adapted microbial communities that are in constant competition for substrates and nutrients. Their natural distribution, interactions and responses to fluctuating environmental conditions are often impossible to simulate in laboratory studies. Using biogeochemical iron redox cycling as an example, we suggest the application of a conceptual framework to improve our understanding of the principal functioning of (geo)microbial ecosystems. Abstract.Our knowledge on how microbial ecosystems function profits from the support of biogeochemical concepts which describe the cycling of elements through various geochemical gradients. Using the example of the iron cycle in freshwater sediments, we propose a theoretical framework that describes the dynamic interactions between chemical and microbial FeII oxidation and FeIII reduction, their spatial location and how they are affected by changing environmental conditions. This contribution emphasises the complexity ecological research faces when dealing with heterogeneous and dynamic natural systems. Our concept aims to provide further insights into how flows of energy and matter are controlled during microbial and chemical Fe redox transformations and how various key variables, such as substrate availability and competition as well as thermodynamic and kinetic parameters, affect flow directions.
Iodine speciation in marine aerosols along a 15000-km round-trip cruise path from Shanghai, China, to the Arctic Ocean
Authors: Xu Siqi , Xie Zhouqing , Li Bing , Liu Wei , Sun Liguang , Kang Hui , Yang Hongxia , Zhang Pengfei
Published: October 2010

Environmental context.Iodine in the atmosphere plays an important role in troposphere ozone destruction and climate change. However, cycling of atmospheric iodine is still poorly understood because of uncertainties in iodine speciation in aerosols. Here we report iodine levels and speciation in marine aerosols collected along a cruise path from Shanghai to the Arctic Ocean.

Abstract.Total iodine (TI) and water-soluble iodine species in the total suspended particle samples collected onboard a round-trip cruise from Shanghai, China to the Arctic Ocean were measured using inductively coupled plasma mass spectrometry and ion chromatography–inductively coupled plasma mass spectrometry respectively. TI and total soluble iodine (TSI) levels varied considerably both spatially and temporally over the length of the voyage. The maximum iodine levels occurred in the Arctic Ocean in September, whereas the minimum levels occurred in the Western and Northern Pacific Ocean in July. Iodate (IO3
–) was found to be the dominant species in most samples, accounting for 57.8% of TSI on average, whereas iodide and soluble organic iodine only accounted for 16.8% of TSI on average. There was also a significant fraction of insoluble iodine. This finding confirms model predictions of atmospheric iodine speciation, i.e. the predominant iodine species is iodate rather than iodide.
Structural insight into the mechanisms of enveloped virus tethering by tetherin
Authors: Yang Haitao , Wang Jimin , Jia Xiaofei , McNatt Matthew W. , Zang Trinity , Pan Baocheng , Meng Wuyi , Wang Hong-Wei , Bieniasz Paul D. , Xiong Yong
Published: October 2010

Tetherin/BST2 is a type-II membrane protein that inhibits the release of a range of enveloped viruses, including HIV-1. Here we report three crystal structures of human tetherin, including the full-length ectodomain, a triple cysteine mutant and an ectodomain truncation. These structures show that tetherin forms a continuous alpha helix encompassing almost the entire ectodomain. Tetherin helices dimerize into parallel coiled coils via interactions throughout the C-terminal portion of the ectodomain. A comparison of the multiple structures of the tetherin dimer reveals inherent constrained flexibility at two hinges positioned at residues A88 and G109. In the crystals, two tetherin ectodomain dimers associate into a tetramer by forming an antiparallel four-helix bundle at their N termini. However, mutagenesis studies suggest that the tetrametric form of tetherin, although potentially contributing to, is not essential for its antiviral activity. Nonetheless, the structural and chemical properties of the N terminus of the ectodomain are important for optimal tethering function. This study provides detailed insight into the mechanisms by which this broad-spectrum antiviral restriction factor can function.