Abstracts of the10th Meeting of the Italian Peripheral Nerve Study Group

s of the10th Meeting of the Italian Peripheral Nerve Study Group Verona, March 17–19, 2006 PHENOTYPICAL AND GENOTYPICAL HETEROGENEITY OF CHARCOT-MARIE-TOOTH DISEASE TYPE 2A ASSOCIATED WITH THE MITOFUSIN 2 GENE (MFN2) Angiari C, Cavallaro T, Ferrarini M, Taioli F, Cabrini I, Ferrari S, Fabrizi GM, Rizzuto N. Department of Neurological and Visual Sciences, Section of Clinical Neurology, University of Verona, Italy. The mitofusin 2 gene (MFN2) encodes a GTPase protein localized in the mitochondrial outer membrane that regulates the fusion, architecture, and metabolism of mitochondria. A recent report indicated that the MFN2-related Charcot-Marie-Tooth disease (CMT) type 2A accounts for approximately 20% of all cases with CMT2 (Lawson et al., 2005), often manifesting features of multisystem involvement such as pyramidal signs (Zhu et al., 2005) or optic atrophy (Zuchner et al., 2006). We investigated the role of MFN2 in 80 index cases with clinical and electrophysiological criteria of CMT2 without mutations of the myelin protein zero (P0), connexin 32 (C 32) and neurofilament light-chain subunit (NEFL); 22 cases had dominant inheritance while the remaining were sporadic without laboratory evidences of acquired neuropathy. Exons 3–19 encoding the full-length protein were scanned by denaturing high performance liquid chromatography (DHPLC) with related exon-intron boundaries; positive amplicons were dissected by nucleotide sequencing. We identified 3 heterozygous mutations in the GTP-ase domain in three cases out 80 (3.75%). A novel Arg259Cys substitution (c.775C > T) in a threegeneration pedigree was associated with a mild-tomoderate syndrome and onset in the second decade of life. A novel Val273Leu (c.817G > T) substitution caused a severe disease in a sporadic patient with early infantile onset and a clinical and neurophysiological selective involvement of the lower limbs. An Arg280His (c.838G > A) substitution led to a severe syndrome of both the lower and upper limbs in a sporadic patient with lateinfantile onset. Retrospective examinations ruled out pyramidal signs and optic neuropathy. In the index cases sural nerve biopsies disclosed loss of large myelinated fibers, clusters of regenerating fibers with simple onion bulbs and uniformly shortened internodes on teased fibers. The report emphasizes the genetic heterogeneity of CMT2 and the phenotypical variability of CMT2A. ELECTROPHYSIOLOGICAL PARAMETERS ASSOCIATED WITH RESPONSE TO IVIG IN MULTIFOCAL MOTOR NEUROPATHY Ardolino GL,Terenghi F, Gallia F, Casellato C, Bossi B, CarpoM, Nobile-Orazio E. Neurologia 2, IRCCS Istituto Clinico Humanitas, Centro Dino Ferrari, Dip. Scienze Neurologiche Università di Milano, Rozzano (Mi), Italy. Multifocal motor neuropathy (MMN) is a relatively rare disorder characterized by focal conduction blocks along motor fibres leading to weakness in the territory of individual nerves. Although its pathogenesis is not clear, MMN is thought to arise from dysimmune mechanisms and responds to treatment with intravenous immunoglobulin (IVIg). The objective of this study was to evaluate the effect of the first administration of high dose IVIg on electrophysiological parameters in MMN. We tested 18 clinically affected nerves from 9 subjects with newly diagnosed MMN before and 7–20 days after the first administration of IVIg (2 g/kg). Only nerves with clinical improvement (at least 1 point in the Medical Council Research scale) were included in the analysis. Distal and proximal CMAP amplitude, conduction velocity (CV), distal latency (DL), and conduction block (CB) were evaluated. CB was considered only in distal tract (i.e., elbow-wrist). At baseline, 10 nerves had abnormal distal and 13 proximal CMAP amplitudes. No significant change in their amplitude was detected after IVIg administration. Seven nerves had CV below lower normal limits at baseline examination including five with definite and two with possible CB. CV increased in six nerves after IVIg (mean 129.4% 13.5; range 84–190%) and slightly decreased in one nerve with a greater than 90% CB at baseline. CB remained unchanged despite clinical improvement in five nerves, improved by at least 20% in two nerves and slightly worsened (8%) in one. No correlation between CV and CB changes was detected. Only 3 of 17 nerves had abnormal DL at baseline and none improved after therapy. Improvement after IVIg therapy has been inconsistently associated with reduction of CB also because the correlation between clinical and electrophysiological improvement in individual nerves has been seldom analysed. In this study only CV, which is a marker of fast conducting fibres, but not CB, consistently improved in parallel with clinical improvement after IVIg. These findings suggests that the improvement of CV or, as recently reported, temporal dispersion may indicate an improved nerve conduction which may explain response to IVIg treatment despite the persistence of CB. Journal of the Peripheral Nervous System 11:179–208 (2006) 2006 Peripheral Nerve Society 179 Blackwell Publishing PROGRESSIVE MOTOR NEURON DISEASE IN TWO PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV-1) INFECTION: A CAUSAL RELATIONSHIP? Ariatti A,Tassone G, Girolami F, Galassi G. Clinica Neurologica, Dipartimento di Neuroscienze , Nuovo Ospedale S. AgostinoEstense, Baggiovara, Modena, Italy. Segmental forms of motor neuron diseases such as brachial amyotrophic diplegia (BAD) result in weakness and atrophy of upper extremities usually in absence of bulbar, lower limb involvement, pyramidal signs, sphincter dysfunctions, and sensory loss. We describe two HIV-1seropositive patients affected by a motor neuron disorder which could be defined as BAD (case 1) whereas in case 2 bulbar muscles were also involved. A 50-year-old man noticed progressive symmetric weakness and wasting of shoulders and arms. On examination, the patient exhibited peculiar posture of both hands hanging loosely at his sides with visible fasciculations. Reflexes were absent in the upper extremities and normal in the lower. Case 2 presented with diplopia, dysarthria, dysphagia, similar symmetric weakness and atrophy. Neurological examination showed an additional paresis of the 6th, right 7th, 9th, and right 12th cranial nerves with tongue atrophy. In both cases routine blood tests and search for anti-GM1 antibodies were negative. In Case 1 creatine kinase was elevated (361 mU/ml, n.v. below 195); test for HIV-1 was positive with RNA level of 144.920 copies/ml and CD4 count 403/ mm. In Case 2 the test for HIV-1 was positive with RNA level of 25.357 copies/ml and CD4 count 90/mm. HIV viral load was 58.093 copies/ml. CSF showed increased protein content (181 mg/dl) and 15 polymorphonuclear cells/mm. Electrophysiology showed in case 1 low amplitude of action potentials and reduced motor velocity without conduction block. Motor velocity of case 2 was normal. On EMG there were acute and chronic neurogenic changes in the upper and lower limbs of both. Patient disability remained stable over two years under retroviral therapy. Although there is no proof of a definite relationship between HIV infection and motor neuron disorders, it is necessary to outline such an occurrence. The disorder may represent one end of the spectrum of motor neuron diseases occurring in association with HIV-1 infection. CLINICAL AND MOLECULAR CHARACTERIZATION OF PATIENTS WITH CHARCOT-MARIE-TOOTH NEUROPATHIES BenedettiS,CovielloS,Spiga I, FazioR,DacciP,Menditto I, Carrera P, Comi G, Ferrari M, Bolino A, Quattrini A, Previtali S. Laboratorio di Biologia Molecolare Clinica, Diagnostica e Ricerca; Dulbecco Telethon Institute; Dipartimento di Neurologia; Unità di Genomica per la Diagnosi di Patologie Umane, IRCCS San Raffaele, Milano,