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Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.

The purpose of this study was to quantitate motor performance in 196 genetically confirmed steroid-naïve boys with Duchenne muscular dystrophy (DMD), to evaluate the test-retest reliability of measures of motor performance in young DMD boys, and to assess correlations among the different functional outcomes including timed tests. Boys aged 4-7 years were recruited in the FOR-DMD study, a comparative effectiveness study of different steroid regimens in DMD. Eligible boys had to be able to rise from the floor independently and to perform pulmonary function testing consistently. The boys were evaluated with standardized assessments at the screening and baseline visits at 32 sites in 5 countries (US, UK, Canada, Italy, Germany). Assessments included timed rise from floor, timed 10 m walk/run, six-minute walk distance, North Star Ambulatory Assessment (NSAA) and forced vital capacity (FVC). Mean age at baseline was 5.9 years (range 4.1-8.1 years). Test-retest reliability was high for functional assessments, regardless of time lag between assessments (up to 90 days) and for the majority of age groups. Correlations were strong among the functional measures and timed tests, less so with FVC. Physiotherapy measures are reliable in a young, steroid-naïve population and rise from floor velocity appears to be a sensitive measure of strength in this population.

Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN > 12 weeks), and outside of these approved specialist centers (HPN

Background : In France, home parenteral nutrition (HPN) is managed by two parallel healthcare systems : in approved specialist centers (HPN12 weeks), and outside of these approved specialist centers (HPN12 weeks). Objective : To prospectively evaluate infectious and vascular complications in adult cancer patients undergoing HPN administered via a central venous line, outside of approved specialist HPN centers. Methods : Our observational prospective study included adult patients with cancer, hospitalized for 48 hours or more, and under HPN. They had a WHO performance status of ≤ 2 and had had a nutritional consultation before discharge. Results : 25 patients were included in the study, with a median age of 63 years [19–74]. Weight loss of ≥ 5% was reported in 79% of patients. The Ingesta score was7 in 96% of cases. 87% of patients presented chill or body temperature variation episodes, with a median of 2 episodes [1–6] per patient. The median delay between end of hospitalization and the first chill episode was 11 days [1–85]. A vascular complication (obstruction without thrombosis) was reported in one patient. Discussion : This high number of infectious episodes requires improvement of patient care when it comes to strictly adhering to the recommendations. Getting the approved specialist HPN centers to work together and share care protocols could be the first important step.

Resume Objectif Les tumeurs gliales intramedullaires de l’adulte sont des tumeurs rares representant moins de 4 % de l’ensemble des tumeurs du systeme nerveux central. L’etude retrospective que nous rapportons, avait pour objectifs d’etudier l’histoire naturelle et les modes de prise en charge de ces tumeurs. Materiel et methodes Elle a concerne 332 patients : 72 % d’ependymomes, dont 94 % de bas grade, 24 % d’astrocytomes, dont 29 % de haut grade, 2,4 % de gliomes mixtes et 1,7 % d’oligodendrogliomes. Resultats L’âge au diagnostic etait de 42,4 ans pour les ependymomes avec une forte predominance masculine, 39,6 ans pour les astrocytomes. La douleur representait le symptome revelateur le plus frequent. Une biopsie chirurgicale, seule, etait effectuee dans pres de 20 % des astrocytomes, alors que plus de 80 % des ependymomes beneficiaient d’une exerese. Les traitements adjuvants, radiotherapie et chimiotherapie, etaient reserves aux tumeurs malignes, surtout quand il s’agissait d’ependymomes. Le taux de survie a 5 ans etait de 76,8 % pour les astrocytomes et de 94,5 % pour les ependymomes. Conclusion L’histologie, le score fonctionnel preoperatoire, le grade, sont des facteurs pronostiques retrouves dans cette serie. Si pour les ependymomes la prise en charge chirurgicale essentiellement est bien codifiee, la question d’une sous-utilisation des traitements adjuvants pour les astrocytomes est posee.

Resume De plus en plus de patients obeses ou en surpoids sont pris en charge en oncologie. L’evaluation nutritionnelle de ces patients comprend l’indice de masse corporelle, le poids et son evolution et l’echelle visuelle des ingesta. L’etude de la composition corporelle semble prometteuse mais n’est pas realisee en pratique courante. Le pronostic des patients obeses ou en surpoids est souvent meilleur que pour les autres patients mis a part dans le cancer du sein ou en cas de sarcopenie associee. Pour le calcul des besoins nutritionnels, le poids utilise sera celui calcule pour un indice de masse corporelle theorique compris entre 25 et 30 kg/m 2 . En oncologie, l’adaptation des doses de chimiotherapie reste une question en suspens avec des risques de sur- ou de sous-dosage, necessitant des etudes complementaires. Dans le cadre de la radiotherapie, des difficultes techniques peuvent etre rencontrees pour certains patients obeses et des toxicites plus marquees en cas d’irradiation mammaire si le volume du sein est important. Les recommandations de prise en charge nutritionnelle sont les memes que pour les patients non obeses, notamment dans les cancers des voies aerodigestives superieures ou dans le cancer colorectal. Une prise en charge nutritionnelle precoce est essentielle pour les patientes avec un indice de masse corporelle superieur a 25 kg/m 2 , traitees pour un cancer du sein. En situation palliative, si des difficultes techniques existent pour les patients avec une obesite majeure, il n’y a pas d’etudes dans ce cas de figure.

Background Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy. Since its first description, more than 120 amyloidogenic transthyretin mutations have been reported with various geographic distributions and associated with a wide range of phenotypes involving the peripheral nerve, the heart, the gastrointestinal tract, the eyes, the central nervous system, or the kidneys. In some cases of transthyretin amyloidosis, the first clinical manifestation is vitreous opacity. Case presentation A 46-year-old Bangladeshi woman presented with vitreous amyloidosis and progressive autonomic neuropathy of the digestive tract as initial clinical manifestations, with no clinical evidence of cardiac, renal, central nervous system, or peripheral nerve dysfunction. A novel transthyretin mutation, p.Gly87Arg, was identified in the heterozygous state in this proband of Bangladeshi origin. Histological examination of accessory salivary glands and gastric biopsies revealed Congo-red-positive deposits. Laser microdissection of salivary gland Congo-red deposits and tandem mass spectrometry-based proteomic analysis identified the mutated transthyretin peptide containing the arginine residue at position 87 of the mature protein. Conclusions Vitreous amyloidosis should be considered a differential diagnosis of uveitis, in particular transthyretin amyloidosis. Proteomics data from our case, consistent with the genetic findings, highly suggests that this new p.Gly87Arg variant is amyloidogenic. Here, we described the second case of transthyretin amyloidosis reported in a Bangladeshi patient.

Nerve enlargement has early been recognized in CIDP and plexus MRI hypertrophy has been reported in typical CIDP cases. Our aim is to determine plexus MRI value in the diagnosis of CIDP with an initial atypical presentation, which, up to now, has not been demonstrated. Retrospective study of 33 consecutive patients suspected of CIDP. Plexus MRI was performed on the most affected territory (brachial or lumbar). Were assessed: plexus trophicity, T2-STIR signal intensity and gadolinium enhancement. Final CIDP diagnosis was made after comprehensive workup. A histo-radiological correlation was performed. Final CIDP diagnosis was made in 25 (76%) including 21 with initial atypical clinical presentation. Eleven CIDP patients (52%) with initial atypical clinical presentation had abnormal plexus MRI including 9 suggestive of CIDP (43%) and none of the patients with an alternative diagnosis. Hypertrophy of the proximal plexus and/or extraforaminal roots was found in 8 cases and Gadolinium enhancement in 2 cases. Abnormalities were more frequent on brachial (86%) than lumbosacral MRIs (29%) and asymmetrical (72%) and most often associated with histological signs of demyelination. The nerve biopsy was suggestive of CIDP in 9/13 patients with normal MRI. Plexus MRI seems useful in the diagnostic strategy of patients with suspicion of CIDP with atypical presentation. Nerve biopsy remains important when other investigations are inconclusive.

Resume Introduction En France coexistent deux systemes de soins pour les patients sous nutrition parenterale a domicile (NPAD) : les centres experts (NPAD > 12 semaines) et la nutrition hors centre expert (NPAD Objectif de l’etude Evaluer les complications infectieuses et vasculaires chez l’adulte atteint d’un cancer et beneficiant d’une NPAD sur voie veineuse centrale hors centre expert. Methode Notre etude observationnelle et prospective a inclus des adultes avec un cancer, hospitalises plus de 48 heures sous NPAD, avec un indice de performance (Perfomans status, OMS) ≤ 2 et apres une consultation nutritionnelle. Principaux resultats Vingt-cinq patients ont ete inclus dans l’etude. L’âge median etait de 63 ans (19–74). Une perte de poids ≥ 5 % a ete observee pour 79 % d’entre eux. Le score ingesta etait Discussion Le taux eleve d’episodes infectieux necessite de revoir la prise en charge des patients dans le respect des recommandations. Un rapprochement des centres experts de NPAD et le partage des protocoles semblent constituer une premiere etape indispensable. La place des infirmiers experts est probablement essentielle.

Familial transthyretin amyloidosis (ATTR) is a rare, life-threatening, autosomal dominant disease involving mainly the heart and the peripheral nervous system due to a point mutation of the transthyretin ( TTR ) gene. By removing the main source of the mutated TTR , liver transplantation (LT) has

Resume Objectifs Les fentanyl transmuqueux, recemment commercialises, permettent de s’adapter precisement aux acces douloureux paroxystiques, sous reserve que la douleur chronique soit controlee par un traitement de fond adapte. L’objectif de cette analyse etait de realiser un etat des lieux des pratiques medicales et infirmieres sur l’utilisation de deux fentanyl transmuqueux et de recueillir l’opinion des patients. Methodes Deux questionnaires sur l’utilisation de deux fentanyl transmuqueux (un sublingual, A, et un nasal, B) ont ete utilises : un pour les infirmiers et un pour les patients. Parallelement, le dossier patient a ete exploite, ainsi que les pancartes de soins. Resultats Sur six mois, 24 prescriptions ont ete retrospectivement analysees (17 pour le produit A, sept pour le B). Quatre etaient hors autorisation de mise sur le marche. Seulement trois prescriptions respectaient le schema d’administration (titration, pas d’intervalle fixe, delai de readministration entre 15 et 30 min). Neuf patients etaient interrogeables. Ils ont attribue une note globale moyenne de 2,63 sur 4 (efficacite, rapidite d’action, facilite de prise, ouverture du conditionnement). Au niveau des services, 15 infirmieres ont ete sollicitees, huit savaient qu’elles pouvaient readministrer une seconde dose. Les infirmiers avaient un avis globalement positif sur le medicament, sauf sur l’ouverture du conditionnement (note moyenne de 2 sur 4). Conclusion Cette evaluation revele un mesusage des fentanyl transmuqueux, aussi bien par les equipes medicales que soignantes et doit etre consideree comme une etude de faisabilite. Une nouvelle etude serait a realiser sur une plus grande cohorte de patients.

The association of Charcot-Marie-Tooth (CMT) disease with renal dysfunction is uncommon but has long been recognized in several families. Recently, mutations in the INF2 gene, which encodes inverted formin-2, were identified in patients with focal segmental glomerulosclerosis and a dominant intermediate form of CMT (CMTDIE, OMIM #614455). We describe the pathologic lesions of nerve biopsies from 6 patients with INF2-related CMTDIE. There were 4 females and 2 males; ages were from 12 to 47 years; durations between neuropathy onset and biopsy were from 2 to 37 years. Clinical phenotypes were similar to those seen in other forms of CMT disease, but there was always an associated proteinuria (and later renal failure). Motor median nerve conduction velocities were in the range of intermediate CMT disease. Pathologic lesions suggested chronic demyelination and remyelination associated with progressive axonal loss. By electron microscopy, we observed unusual whorl-like proliferations of flattened Schwann cell cytoplasm and anomalies of unmyelinating Schwann cell cytoplasm with supernumerary elongated extensions similar to those described in CMT4C. We also observed abnormal accumulation of β-actin in the cytoplasm of Schwann cells. Our results suggest that these lesions reflect a global disorder of the actin cytoskeleton in Schwann cells and that CMTDIE is the first peripheral nerve disorder associated with a Schwann cell actinopathy.

BACKGROUND: The aim of this study was to correlate MRI features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The MRI characteristics of 50 AO patients enrolled in the French national network for high-grade oligodendroglial tumors were analyzed. The genomic profiles and IDH mutational statuses were assessed using high-resolution single-nucleotide polymorphism arrays and direct sequencing, respectively. The gene expression profiles of 25 1p/19q-codeleted AOs were studied on Affymetrix expression arrays. RESULTS: Most of the cases were frontal lobe contrast-enhanced tumors (52%), but the radiological presentations of these cases were heterogeneous, ranging from low-grade glioma-like aspects (26%) to glioblastoma-like aspects (22%). The 1p/19q codeletion (n = 39) was associated with locations in the frontal lobe (P = .001), with heterogeneous intratumoral signal intensities (P = .003) and with no or nonmeasurable contrast enhancements (P = .01). The IDH wild-type AOs (n = 7) more frequently displayed ringlike contrast enhancements (P = .03) and were more frequently located outside of the frontal lobe (P = .01). However, no specific imaging pattern could be identified for the 1p/19q-codeleted AO or the IDH-mutated AO. Within the 1p/19q-codeleted AO, the contrast enhancement was associated with larger tumor volumes (P = .001), chromosome 9p loss and CDKN2A loss (P = .006), genomic instability (P = .03), and angiogenesis-related gene expression (P < .001), particularly for vascular endothelial growth factor A and angiopoietin 2. CONCLUSION: In AOs, the 1p/19q codeletion and the IDH mutation are associated with preferential (but not with specific) imaging characteristics. Within 1p/19q-codeleted AO, imaging heterogeneity is related to additional molecular alterations, especially chromosome 9p loss, which is associated with contrast enhancement and larger tumor volume.

Introduction et but de l’etude Les patients ayant une nutrition enterale ou parenterale demandent a etre mieux accompagnes dans l’acceptation et la gestion de leur nutrition artificielle afin d’ameliorer leur bien-etre. L’Education therapeutique du patient (ETP) est reconnue comme une methode efficace pour y parvenir. Pour autant, en France, tres peu de programmes existent sur le sujet. C’est pourquoi, 3 equipes specialisees de l’Institut regional du cancer de Montpellier (ICM) et des patients ont concu un programme intitule « Mon energie connectee ! »–programme d’education therapeutique en nutrition artificielle. Materiel et methodes Le programme « Mon energie connectee » a ete formalise de juin a aout 2017. Une enquete par entretiens semi-diriges aupres de 21 patients avait initialement ete realisee jusqu’a saturation des donnees. Les patients interroges devaient etre porteurs d’un des quatre types de nutrition artificielle proposes a l’ICM : nutrition parenterale, nutrition enterale par sonde naso-gastrique, par gastrostomie et par jejunostomie. Une analyse qualitative des donnees par regroupement en champ semantique a ete realisee pour categoriser les problemes et les ressources des patients. Dans un deuxieme temps, un groupe de travail constitue de 5 dieteticiens, 2 medecins nutritionnistes, 1 medecin generaliste, 1 cadre infirmier, 1 infirmiere experte en nutrition, 3 specialistes en ETP et 5 patients a identifie les besoins educatifs selon la methode issue des travaux de Martin et Savary. Ce groupe a ensuite concu un programme d’ETP, en combinant les donnees de l’analyse qualitative et de la litterature. Resultats et analyse statistique L’analyse de l’enquete a permis d’identifier 35 problemes et 46 ressources regroupees respectivement en 6 et 7 dimensions. 24 besoins educatifs ont ainsi ete definis pour concevoir le programme « Mon energie connectee ! ». Celui-ci comporte un Bilan educatif partage (BEP) individuel, 6 seances educatives individuelles et/ou collectives (dont 2 optionnelles) pour le patient ou son entourage et une seance individuelle de Bilan educatif final (BEF). Chaque seance dure entre 30 et 120 minutes et est animee par un professionnel specialiste de la nutrition forme en ETP. Un outil de partage a ete concu pour les professionnels et permet d’editer un BEP remis au patient et visible, avec son accord, dans son dossier medical informatise. Les outils patients sont en cours de realisation. Conclusion Ce travail a permis d’identifier 24 besoins educatifs et un programme ETP a ete concu pour y repondre en fonction du degres d’autonomie desire par le patient. La demarche analytique en ETP, a permis de valoriser le vecu des patients porteurs d’une nutrition artificielle et de les inclure dans la conception du programme. L’evaluation sur le terrain permettra de valider son efficacite. L’enjeu principal est d’integrer une approche educative formalisee dans les futurs standards de prise en charge pour la nutrition artificielle.

Intramedullary tumors constitute approximately 5% of spinal tumors and about 80% are of neuroglial origin. We reviewed our series of adult patients with spinal neuroglial intramedullary tumors operated on between 1984 and 2011 at the neurosurgical department of Bicetre hospital. The histopathological records for 196 patients were retrospectively analyzed. The majority of tumors were ependymomas (68%) and astrocytomas (27.5%). The importance of a proper and detailed neuropathological diagnosis is the key to define patient management. The available literature data about the genetic profiles of these rare tumors are summarized and reviewed.

International audience; OBJECTIVES This study sought to compare techniques evaluating cardiac dysautonomia and predicting the risk of death of patients with hereditary transthyretin amyloidosis (mATTR) after liver transplantation (LT). BACKGROUND mATTR is a multisystemic disease involving mainly the heart and the peripheral nervous system. LT is the reference treatment, and pre-operative detection of high-risk patients is critical. Cardiovascular dysautonomia is commonly encountered in ATTR and may affect patient outcome, although it is not known yet which technique should be used in the field to evaluate it. METHODS In a series of 215 consecutive mATTR patients who underwent LT, cardiac dysautonomia was assessed by a dedicated clinical score, time-domain heart rate variability, (123)-meta-iodobenzylguanidine heart/mediastinum ((123)-MIBG H/M) ratio on scintigraphy, and heart rate response to atropine (HRRA). RESULTS Patient median age was 43 years, 62% were male and 69% carried the Val30Met mutation. Cardiac dysautonomia was documented by at least 1 technique for all patients but 6 (97%). In univariate analysis, clinical score, (123)-MIBG H/M ratio and HRRA were associated with mortality but not heart rate variability. The (123)-MIBG H/M ratio and HRRA had greater area under the curve (AUC) of receiver-operating characteristic curves than clinical score and heart rate variability (AUC: 0.787, 0.748, 0.656, and 0.523, respectively). Multivariate score models were then built using the following variables: New York Heart Association functional class, interventricular septum thickness, and either (123)-MIBG H/M ratio (SMIBG) or HRRA (S-atropine). AUC of S-MIBG and S-atropine were greater than AUC of univariate models, although nonsignificantly (AUC: 0.798 and 0.799, respectively). Predictive powers of S-MIBG, S-atropine, and a reference clinical model (AUC: 0.785) were similar. CONCLUSIONS Evaluation of cardiac dysautonomia is a valuable addition for predicting survival of mATTR patients following LT. Among the different techniques that evaluate cardiac dysautonomia, (123)-MIBG scintigraphy and heart rate response to atropine had better prognostic accuracy. Multivariate models did not improve significantly prediction of outcome. (C) 2016 by the American College of Cardiology Foundation.

Peripheral nerve hyperexcitability (PNH) is one of the distal peripheral neuropathy phenotypes often present in patients affected by type 2 diabetes mellitus (T2DM). Throughin vivoandex vivoelectrophysiological recordings in db/db mice, a model of T2DM, we observed that, in addition to reduced nerve conduction velocity, db/db mice also develop PNH. By using pharmacological inhibitors, we demonstrated that the PNH is mediated by the decreased activity of Kv1-channels. In agreement with these data, we observed that the diabetic condition led to a reduced presence of the Kv1.2-subunits in juxtaparanodal regions of peripheral nerves in db/db mice and in nerve biopsies from T2DM patients. Together, these observations indicate that the T2DM condition leads to potassium channel-mediated PNH, thus identifying them as a potential drug target to treat some of the DPN related symptoms.

International audience; Objective To compare the natural history of familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr, and Ile107Val mutations in France with the classical Portuguese Val30Met FAP. Methods We compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies, and muscle biopsies are reported. We also conducted a comprehensive literature review to further determine the range of phenotypic expression. Results By comparison with Portuguese Val30Met FAP, French Ile107Val, Ser77Tyr, and LateVal30Met FAP showed more rapid and severe disease progression; onset of gait disorders was 3 times more rapid (p 50 years; LateMet30) FAP (p = 0.0005). Other distinctive features relative to the Portuguese patients included atypical clinical presentations, demyelination on nerve conduction studies (p = 0.0005), and difficult identification of amyloid deposits in nerve and muscle biopsies. Interpretation Ile107Val and LateMet30 mutations are associated with the most debilitating and severe FAP ever described, with rapid onset of tetraparesis and shorter median survival. It could be explained by frequent large‐fiber involvement and associated demyelination and more severe axonal loss. These findings have major implications for genetic counseling and patient management as new therapeutic options are being assessed in clinical trials (TTR gene silencing). Ann Neurol 2015;78:901–916

Resume Le vieillissement de la population est une realite demographique, l’incidence des pathologies chroniques augmente avec l’avance en âge, la prevalence de la denutrition s’accroit chez la personne âgee en fonction de l’etat de sante, des conditions de vie, du degre de dependance. Apres quelques rappels sur le statut nutritionnel de la personne âgee, la place de l’evaluation geriatrique est evoquee comme element de pronostic et d’aide a la decision. Si les techniques de nutrition et hydratation artificielle n’ont pas de specificite geriatrique, leur mise en œuvre s’appuie sur le pronostic, les benefices attendus, les termes de la loi dans le respect des souhaits de la personne malade et dans une demarche ethique.

Item does not contain fulltext Nerve biopsy is often the final step in the diagnostic work-up of neuropathies of unknown origin. The aim of this guideline was to prepare an evidence-based guideline on the methods for performing and evaluating nerve biopsy. The panel performed a search of MEDLINE, hand search of bibliographies of the references retrieved, review of the evidence, and reached agreement by consensus. There were not enough formal studies of diagnostic test accuracy to allow evidence-based recommendations of levels A-C for most questions. The panel summarized the class IV evidence and reached agreement by consensus on the following recommendations: (1) Nerve biopsy should not be performed before adequate clinical, electrophysiological, and laboratory investigation and only be performed with appropriate informed consent. (2) An interactive working relationship with the relevant disciplines involved and the provision of sufficient clinical information is encouraged. (3) Biopsies should be processed and read by professionals with adequate training and experience. (4) Optimal analysis of nerve biopsy is best performed by laboratories that have the facilities and expertise to prepare and evaluate frozen and fixed sections (cryostat, paraffin, and epoxy sections). (5) Immunohistochemistry, teased fiber analysis, electron microscopy, and morphometry may help clarify the diagnosis in some conditions and should be considered as additional studies. 01 september 2010

Objective To determine the long-term outcome of surgically treated Chiari-related syringomyelia. Methods The medical charts of 157 consecutive surgically treated patients with Chiari-related syringomyelia were retrospectively analyzed. Factors predicting outcome, either clinical or radiological, are discussed, and our results are compared with those of other large series in the literature. Results The study included 74 men and 83 women (age range, 16-75 years; mean age at surgery, 38.3 years). Pain and sensory disturbance were the most frequent initial symptoms. The average duration of preoperative symptoms was 8.2 years. The follow-up period ranged from 82 to 204 months (median, 88 months). At the end of the study, 99 patients (63.06%) had improved, 48 (30.58%) had stabilized, 9 (5.73%) had worsened, and 1 (0.63%) had died during the postoperative period. Factors predicting improvement or stabilization were young age at the time of surgery and clinical signs of paroxysmal intracranial hypertension. Factors associated with a poor outcome were older age at the time of surgery, arachnoiditis, and a clinical feature of long-tract impairment syndrome. The presence of arachnoiditis or of basilar invagination was associated with poor clinical presentation (P = 0.05 and 0.0001, respectively). The extent of the cyst on postoperative magnetic resonance imaging was a predictor of poor clinical outcome (P = 0.002). Conclusion Our results confirmed that surgery is an effective and safe treatment of Chiari-related syringomyelia, with a 90% chance of long-term stabilization or improvement on average. Surgery should be proposed as soon as possible in patients with clearly progressing clinical features.

International audience; Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when associated with autonomic dysfunction.

Objective: Intraspinal grafting procedures using peripheral nerve grafts (PNG) or collagen guidance channels (CGC) have been recently used to treat brachial plexus injuries in humans and spinal cord injuries in animals. This study examined the effects of these procedures in the adult rat. Methods: In adult rats, we performed an avulsion of left C5, C6, and C7 nerve roots, followed by a myelotomy of the left ventrolateral aspect of the spinal cord between C5 and C6. The rats were subsequently assigned to one of three groups: group A (n = 10), no additional procedure; group B (n = 10), implantation of a PNG following myelotomy; group C (n = 10), implantation of a CGC. Clinical evaluation was postoperatively assessed. Rats were euthanized at day 6 or 21. Spinal cord lesions induced by surgery were assessed by measuring depth and rostrocaudal extent. Reactive astrogliosis, as a reaction to neuroglial damage, was assessed by revealing the glial fibrillary acidic protein with immunochemistry method. Results: No animal showed persistent neurological deficit at day 21. The depth and rostrocaudal extent of tissue damage was comparable in all groups at days 6 and 21. At day 6, the astrocytic reaction observed at the myelotomy/implantation site was statistically stronger in group C (CGC). At day 21, the astrocytic reaction became identical in all groups. Conclusion: This study shows that grafting a PNG or a CGC into the spinal cord does not create significant additional iatrogenic effects and can be used in repair strategies to treat nerve root avulsions or spinal cord injuries. © 2006 Wiley-Liss, Inc. Microsurgery, 2006.

Necrotizing vasculitis occurs as a primary phenomenon in connective tissue disorders and cognate fields, including polyarteritis nodosa and the Churg and Strauss syndrome variant, rheumatoid arthritis, systemic lupus and Wegener's granulomatosis. In all these conditions focal and multifocal neuropathy occur as a consequence of destruction of the arterial wall and occlusion of the lumen of small epineurial arteries. Vasculitis may also complicate the course of other conditions ranging from infection with the HIV and with the B and C hepatitis viruses to diabetes and sarcoidosis. Pathologically polymorphonuclear cells are present in the infiltrates of the vessel wall in primary necrotizing vasculitis, while in secondary vasculitis the inflammatory infiltrate is mainly composed of mononuclear cells. In all instances symptomatic vasculitis requires corticosteroid to control the inflammatory process and prevent further ischemic nerve lesions.

The mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is characterized by the association of gastrointestinal and neurological symptoms. It is a rare autosomal recessive mitochondrial disorder with multiple mitochondrial DNA deletions and/or depletion. It is caused by thymidine phosphorylase (TP) gene mutations resulting in a complete abolition of TP activity. We tested 31 unrelated patients presenting either with a complete MNGIE syndrome (8 patients), a severe intestinal pseudo-obstruction (10 patients), and multiple deletions and/or depletion of mitochondrial DNA (13 patients). All the tested patients presenting with a complete MNGIE had increased thymidine levels in plasma and urine, and no TP activity. The group with pseudo-obstruction syndrome had normal or partial reduction of TP activity. We found pathogenic mutations on TP gene only in the MNGIE syndrome group: all the MNGIE patients were compound heterozygous or homozygous for mutations in the TP gene. Eight of these mutations are yet unreported, confirming the lack of genotype/phenotype correlation in this syndrome. Enzymatic activity and thymidine level are thus rapid diagnosis tests to detect MNGIE affected patients prior to genetic testing for patients with gastrointestinal symptoms.

We report on four patients with severe polyneuropathy associated with intestinal pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation. All three were heterozygous for a recessively transmitted double substitution in the TP gene: Glu286Lys/Glu289Ala, Asp156Gly/Leu177Pro and Glu289Ala/Gly387Asp. The fourth patient, who was the only patient of this series with an affected sib, had no oculomotor manifestations, nor T2 hyperdense signals on brain MRI, and no TP gene mutation and or morphological abnormalities of mitochondria on electron microscopic examination. He was the only patient of this series with an affected sib. The three patients with the full MNGIE syndrome died before the age of 30 years. Detailed results of nerve pathology show that severe axonal degeneration is associated with segmental abnormalities of the myelin sheath in this syndrome which appears genetically heterogeneous. Our findings suggest that only ophthalmoplegia and hyperdense signals on cerebral MRI are directly related to the mitochondriopathy.

Background Antiretroviral prevention of mother to child HIV-1 is established but tolerance remains to be assessed. AIM To determine the risk for persistent mitochondrial dysfunction in HIV-uninfected children born to seropositive mothers. Method An exhaustive study in a large prospective cohort with predetermined algorithm of the unexplained symptoms compatible with mitochondrial dysfunction. A total of 2644 of 4392 children were exposed to antiretrovirals. Complementary investigations were carried out on a case-by-case basis using classification with a diagnostic probability scale, based on experience with constitutional diseases. A spontaneous notification register for children not included in the cohort was created. Results Good circumstantial evidence of mitochondrial dysfunction was found for twelve children. Seven were from the cohort. All presented neurological symptoms, often associated with abnormal magnetic resonance image (10 of 12) and/or a significant episode of hyperlactatemia (seven of 12). All had either a profound deficit in one of the respiratory chain complexes (11 of 12) and/or a typical histological pattern (two of 12). All were perinatally exposed to antiretrovirals. None of them had perinatal morbidity that could explain this symptomatology. The 18-month incidence was 0.26% (95% confidence interval, 0.10-0.54) in exposed children, in comparison with the general figure of 0.01% for paediatric neuro-mitochondrial diseases in the general population. Fourteen other children in the cohort, all exposed to antiretrovirals, had unexplained symptoms, mostly neurological, for which one of the possible differential diagnoses was mitochondrial dysfunction. Close similarities in clinical, neuroradiological and histological findings strongly suggest a common pathological process in all these 26 children. Conclusion Children exposed to nucleoside analogues during the perinatal period are at risk of a neurological syndrome associated with persistent mitochondrial dysfunction.

Besides the common distal symmetrical sensory-motor polyneuropathy (DSP) that is often associated with autonomic dysfunction, diabetic patients may develop multifocal sensory-motor deficits (MDN) secondary to roots, plexus and nerve trunk involvement. Nerve ischaemia has been suggested as a common mechanism for the different patterns of diabetic neuropathies, yet the important clinical differences that exist between DSP and MDN suggest concurrent factors. In order to learn more on the subject, we prospectively studied 22 consecutive diabetic patients with MDN, for which other causes of neuropathy were excluded by appropriate investigations, including biopsy of a recently affected sensory nerve. Three patients had a relapsing course, and the others an unremitting subacute-progressive course. Painful MDN progressed over 2-12 months. The neurological deficit predominated in distal lower limbs which were involved in all patients, unilaterally in seven, bilaterally in the others, with an asynchronous onset in most cases. In addition, a proximal deficit of the lower limbs was present on one side in seven patients, and on both sides in six. Thoracic radiculoneuropathy was present bilaterally in two patients, and unilaterally in one. The ulnar nerve was involved in one patient, and the radial nerve in two. The CSF protein ranged from 0.40 to 3.55 g/l; mean: 0.87 g/l. Electrophysiological testing showed severe, multifocal, axonal nerve lesions in all cases. Asymmetrical axonal lesions were found in all nerve specimens. The mean density of myelinated axons was reduced to 1340 +/- 1070 per mm(2) of endoneurial area versus 8370 +/- 706 myelinated fibres/mm(2) in controls. The mean density of unmyelinated fibres was reduced to 5095 +/- 6875 per mm(2) (extremes: 0-26 600). On teased fibre preparations, 34 +/- 31% of the fibres were at different stages of axonal degeneration (extremes 0-99%); 7 +/- 6% of the fibres showed segmental demyelination or remyelination. Necrotizing vasculitis of perineurial and endoneurial blood vessels were found in six patients. Endoneurial seepage of red cells was present in 11 specimens, and endoneurial haemorrhage in five. Ferric iron deposits that characterize previous bleeding were found in seven patients, including two who had no red cells in the endoneurium. Perivascular mononuclear cell infiltrates were present in the nerve specimens of 21 out of 22 patients, prominently in four patients. In comparison, nerve biopsy specimens of 30 patients with severe distal symmetrical diabetic polyneuropathy showed mild epineurial mononuclear cell infiltrate in one patient and endoneurial seepage of red cells in another. We conclude that MDN is related to pre-capillary blood vessel involvement in elderly diabetic patients with a secondary inflammatory response.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endoproteinases that play an important role in inflammation and tissue degradation. MMP-9 and MMP-2 are gelatinases that have been implicated in the degradation of the blood-brain or blood-nerve barrier. We present an immunohistochemical study on 11 nerve biopsy samples of inflammatory and non-inflammatory polyneuropathies. Perineurium and endothelium were positive for MMP-2 in all tissue sections. In addition, there was a specific up-regulation of MMP-2 in stromal cells of chronic inflammatory demyelinating polyneuropathy (CIDP) and even more in vasculitic neuropathies. MMP-9-positive cells were detected in vessel walls, infiltrates, epineurium and endoneurium of vasculitic neuropathies. In CIDP, MMP-9-positive cells were prominent in vessel walls. Only a few MMP-9-positive cells were detected in noninflammatory controls in blood vessels and adhering to vessel walls. Double staining indicated that the infiltrating cells were T cells and macrophages. Our findings suggest that MMP-9 plays an important role in inflammatory peripheral neuropathy probably as means for inflammatory cell invasion.

We have reviewed the clinical and pathological data of a series of 100 consecutive diabetic patients with symptomatic neuropathy in order to learn more about the causes of neuropathy in this population and on the signs and symptoms that could suggest another cause than diabetes in this setting. After diagnostic procedures, patients were assigned one (at most two) of a final total of 18 different causes of neuropathy. Diabetes accounted for 74 % of the neuropathies in the whole group of patients and for 79 % of those with a fiber length dependent pattern of neuropathy. One third of patients had a neuropathy unrelated to diabetes. As a group, 71 % of the patients presented either a length dependent diabetic polyneuropathy (LDDP) or a proximal diabetic neuropathy (PDN). The LDDP group was biased towards more severely affected patients owing to our specialization. Conversely, most patients with proximal diabetic neuropathy had usual features. Chronic inflammatory demyelinating neuropathy that was diagnosed in 9 % of the patients was the most common non-diabetic cause of neuropathy in this population. We conclude that a short interval between diagnosis of diabetes and the onset of the neuropathy, early motor deficit, markedly asymmetrical deficit and generalized areflexia, which are all uncommon in the LDDP, argue in favor of a non diabetic origin of the neuropathy and should lead to further investigation.

Peripheral neuropathy is a rare, yet treatable manifestation of sarcoidosis, a multisystem disorder characterized by the presence of non-caseating granulomas that are seldom found in nerve biopsy specimens. In order to learn more about the subject, we reviewed our clinical and pathological findings in a series of 11 patients (six men and five women aged 26-83 years) with symptomatic neuropathy associated with characteristic granulomas in nerve biopsy specimens. Only two patients were known to have sarcoidosis before the occurrence of the neuropathy. The neuropathy was focal or multifocal in six patients, including one with a multifocal neuropathy associated with conduction blocks, and one with a multifocal axonal motor deficit. Four patients had a distal symmetrical deficit and one patient had a Guillain-Barre-like syndrome with facial diplegia and respiratory failure. Serum angiotensin-converting enzyme concentration was elevated in only two patients. Epineurial granulomas and perineuritis were present in all nerve specimens. The inflammatory infiltrates invaded the endoneurium, following connective tissue septae and blood vessels, in five patients. Multinucleated giant cells were found in eight patients and necrotizing vasculitis in seven. Inflammatory lesions were associated with variable, asymmetrical involvement of nerve fascicles and axon loss. A muscle specimen was sampled during the same procedure in 10 patients. It showed inflammatory infiltrates and granulomas in nine patients and necrotizing vasculitis in two. Immunolabelling showed a mixed inflammatory infiltrate of T cells (predominantly CD4+ cells) and macrophages, in keeping with a delayed hypersensitivity reaction. In addition to nerve involvement, all patients had at least one other tissue or organ affected, including muscle in nine patients, lungs and/or intrathoracic lymph nodes in eight, skin in three, arthritis in two, and peripheral lymph nodes, stomach and eye in one patient each. Most patients improved on corticosteroids. Two patients remain free of symptoms after 7 years. Severe side-effects of long-term treatment with corticosteroids occurred in two patients, leading to death in one. This study illustrates the wide range of clinical manifestations of sarcoid neuropathy and the frequent association of granulomatous inflammatory infiltrates with necrotizing vasculitis and with silent or symptomatic involvement of other organs.

In order to define clinical patterns of light-chain amyloid (AL) polyneuropathy, we reviewed the data of 24 patients. At diagnosis, the mean duration of the symptoms was 21 months (range,...

BACKGROUND: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AO). METHODS: The histological characteristics of 203 AO patients enrolled in the French national network POLA were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. RESULTS: 1p/19q co-deletion was present in 79% of cases and was associated with alpha-internexin expression (p < 10-4), IDH1/2 mutation (p < 10-4), chromosome 4 loss (p < 10-3), and better overall survival (p < 10-4). Based on mitotic index, microvascular proliferation (MVP) and necrosis, 3 groups of 1p/19q co-deleted AO were identified: AO with more than 5 mitoses per 10-HPF, no MVP and no necrosis, (1), AO with MVP and no necrosis (2) and AO with MVP and necrosis (3). Compared to group 1, group 2 and 3 AO had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared to group 2, group 3 AO had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q co-deleted AO, chromosomal instability was associated with shorter progression free survival (p = 0.024) and shorter overall survival (p = 0.023). CONCLUSIONS: The present study shows that oligodendroglioma with classic histological features remains a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q co-deleted AO are also heterogeneous. Interestingly, mitotic index, MVP and necrosis help to classify them into three groups associated with distinct genomic alterations.

In 1926, Roussy and Levy described a large family whose members manifested an early onset dominantly inherited gait ataxia, pes cavus, and areflexia, which was eventually associated with distal muscle atrophy, postural tremor, and minor sensory loss. Slow nerve conduction and demyelination of nerve fibers with onion bulb formations in nerve biopsy specimens led to the Roussy-Levy syndrome (RLS) being considered a variant of demyelinating Charcot-Marie-Tooth disease (CMT-1). In the present article, we report on the long-term follow-up, on nerve biopsy findings, and on the underlying molecular genetic defect in members of the original family studied by Roussy and Levy. All patients were able to walk during their seventh decade of life. Morphologically, a chronic demyelinating neuropathy with the remarkable aspects of a focally hypertrophic myelin sheath and major loss of myelinated fibers was observed in nerve biopsy specimens of 3 members of this family. Molecular genetic testing identified a previously unknown heterozygous missense point mutation which yielded an Asn131Lys substitution in the extracellular domain of the myelin protein zero (P0). These findings show that the Roussy-Levy family belongs to the CMT-1B subtype and has original morphological and genetic features.

Proximal diabetic neuropathy is a disabling neuropathy that occurs predominantly in non-insulin-dependent diabetic patients over the age of 50. Inflammatory lesions have been found in nerve biopsy specimens of diabetic patients with severe proximal neuropathy or with other patterns of multifocal neuropathy. Some of these patients respond dramatically to treatment with corticosteroids or with other immunomodulators. In this article we report on our findings in 4 additional patients with painful proximal diabetic neuropathy and different patterns of inflammatory nerve lesions whose condition improved spontaneously shortly after performance of a nerve biopsy, without additional treatment.

Three patients with Chediak-Higashi syndrome underwent allogeneic bone marrow transplantation between the ages of 2 years 9 months and 7 years. The outcome was uneventful, with sustained mixed chimerism. No subsequent recurrent infections or hemophagocytic syndrome were observed. At the age of 22 to 24 years, these 3 patients developed a neurologic deficit combining difficulty walking, loss of balance, and tremor. Neurologic evaluation demonstrated cerebellar ataxia and signs of peripheral neuropathy. Moderate axon loss and rarefaction of large myelinated fibers were observed on semithin sections of peripheral nerve. Cerebellar atrophy was detected by cerebral magnetic resonance imaging in 2 patients. We also reviewed the very long-term outcome of the other 11 patients with Chediak-Higashi syndrome who had received bone marrow transplants at our center since 1981. All displayed neurologic deficits or low cognitive abilities.

Objective: Familial amyloid polyneuropathy (FAP) is typically a predominantly sensory and autonomic neuropathy with progressive and late motor involvement leading to death within 10 years. Recently, prognosis was transformed with liver transplantation. Methods: We report an atypical sporadic pure motor and bulbar neuropathy initially mistaken for amyotrophic lateral sclerosis (ALS) in a 50-year-old Malian man. Results: The diagnostic procedure of this clinical purely motor and bulbar neuropathy disclosed amyloid deposits on nerve biopsy which led to the identification of a new Val93Met mutation of transthyretin. This case was also remarkable by its slow progression. Conclusions: This report confirms the motor phenotype of TTR-FAP. That should be considered in the differential diagnosis of motor neuron diseases in order to start accurate therapy. Abbreviations: ALS, amyotrophic lateral sclerosis; CIDP, chronic inflammatory demyelinating polyneuropathy; FAP, familial amyloid polyneuropathy; MRC, medical research council; PMA, progressive muscular atrophy; SALS, sporadic amyotrophic lateral sclerosis; SBMA, spino bulmbar muscular atrophy; TTR, transthyretin

The diffusion model can be transformed into a multicompartment model by means of multi-b factor diffusion-weighted sequences. We adapted a method of statistical analysis of these images and evaluated its performance to distinguish tumor-infiltrated edema from vasogenic edema.Forty-nine patients with infiltrating tumors (38 patients: low to high-grade gliomas) or vasogenic edema (11 patients: metastases, abscess, extra-axial lesions) were studied by multi-b factor diffusion-weighted imaging. Comparison of histological results and morphological and perfusion MRI defined 69 characteristic volumes of interest in the peritumoral edema of 69 distinct infiltrating lesions (40) or lesions inducing vasogenic edema (29).The factorial analysis had a sensitivity of 92.9% and a specificity of 90.6% between tumor-infiltrated and vasogenic edema. Simplified interpretation confined to values of the high and mean diffusivity compartments had a sensitivity of 87.5% and a specificity of 89.2% between strictly tumor-infiltrated edema and vasogenic edema with the advantage of simplified interpretation based on two-color parametric mapping.Discrimination between tumor-infiltrated edema and vasogenic edema can be achieved by means of a 90-s multi-b factor diffusion-weighted sequence and factorial analysis. Simplified visual and quantitative interpretation of the results should also allow integration of multi-b factor analysis into routine neuroradiology practice.

Small fiber neuropathy (SFN) is an important feature of transthyretin familial amyloid polyneuropathy (TTR-FAP). A practical and objective method for the clinical evaluation of SFN is needed to improve the management of this disease. In vivo confocal microscopy (IVCM) of the corneal nerves, a rapid noninvasive technique, may be used as a surrogate marker of SFN.To determine the correlation of SFN with IVCM in patients with TTR-FAP.A prospective, single-center, cross-sectional controlled study was conducted at the French National Reference Center for TTR-FAP from June 1, 2013, to June 30, 2014. Fifteen patients with TTR-FAP underwent a complete neurologic examination, including Neuropathy Impairment Score of the Lower Limbs, hand grip strength, and evaluation of vegetative dysfunction, as well as electrophysiologic studies (nerve conduction and electrochemical skin conductance) and intraepidermal nerve fiber density quantification. Patients and 15 controls (matched for age and sex) underwent ophthalmologic assessments, including corneal esthesiometry and IVCM.Correlation of corneal nerve fiber length (CNFL) with the severity of SFN.Of the 15 patients enrolled in the study, 6 were women (40%); mean (SD) age was 54.4 [13.7] years. The CNFL was shorter in the patients than in controls (13.08 vs 17.57 mm/mm2; difference of 4.49 [95% CI, 0.72 to 8.27]; P = .02). The patients' CNFL correlated with the severity of both autonomic neuropathy assessed by the Compound Autonomic Dysfunction Test (rs = 0.66 [95% CI, 0.22 to 0.87]; P = .008) or electrochemical skin conductance (rs = 0.80 [95% CI, 0.50 to 0.93]; P .001) and sensorimotor neuropathy assessed using the Neuropathy Impairment Score of the Lower Limbs (rs = -0.58 [95% CI, -0.84 to -0.11]; P = .02). Patients with altered sensory nerve action potentials and intraepidermal nerve fiber density had a shorter CNFL (P = .04 and P = .02, respectively). The CNFL could be measured in all patients compared with sensory nerve action potentials (11 patients [73%; 95% CI, 44% to 92%]; P .001) and intraepidermal nerve fiber density (4 patients [27%; 95% CI, 8% to 55%]; P .001).In these 15 patients with TTR-FAP, IVCM measurement permitted rapid, noninvasive evaluation of small-fiber alterations in patients and could be used to assess SFN in this setting. The CNFL could be measured in all patients, thus avoiding the floor effect seen with other neuropathy measures. Longitudinal studies with more cases evaluated are needed to define the place of IVCM in monitoring patients with TTR-FAP.

As amyloid neuropathies have benefited from recent major progress, this review is timely and relevant.The main recent articles on amyloid neuropathy cover its description, methods for diagnosis and therapies. Varied clinical presentations are described in transthyretin (TTR)-familial amyloidosis with polyneuropathy (FAP) and light chain amyloid neuropathy. Mass spectrometry is able to identify the biochemical nature of amyloidogenic protein in nerve biopsy and skin biopsy samples for diagnosis of small fiber polyneuropathy. Both nerve biopsy and TTR gene sequencing are important to identify sporadic cases of amyloid neuropathy. Nerve biopsy is useful in demonstrating the amyloid origin of neuropathies developing after domino liver transplant recipients. Liver transplantation improves long-term survival in Met30 TTR-FAP. Factors recognized as leading to cardiomyopathy progression or heart involvement after liver transplantation are late disease onset and fibril composition. Combined heart and liver transplantation is recommended in severe restrictive cardiomyopathy. Antiamyloid drugs are emerging: tafamidis, a TTR stabilizer, showed in a phase III controlled study its ability to slow stage 1 FAP progression. Other strategies are emerging for TTR-FAP (combination doxycycline-tauroursodeoxycholic acid, small interfering RNA, antisense oligonucleotide, monoclonal antibody antiserum amyloid P component). For light chain neuropathy, intensive chemotherapy may be helpful.There is better recognition of amyloid neuropathies, and hope for enrolling patients with FAP in future clinical trials testing new antiamyloid drugs.

International audience; We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β(2)-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β(2)-microglobulin, the affected members of this kindred had normal renal function and normal circulating β(2)-microglobulin values. The Asp76Asn β(2)-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β(2)-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β(2)-microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding.

The aim of this study was to describe misleading lower limb mono radiculopathy revealing peripheral nerve vasculitis. Retrospective review of eight patients with biopsy confirmed vasculitis presenting as mono-radicululopathy in a tertiary referral centre dedicated to patients with rare peripheral neuropathies. Patients presented with chronic (6/8) or acute (n = 2) radiculopathy in L4, L5 or S1 territories associated with subtle systemic signs. A diagnostic workup was performed because of secondary motor deficit, the absence of clear radicular compression or failure of initial treatment focused on pain relief. In all, nerve conduction studies showed signs of asymmetrical axonal peripheral neuropathy (mononeuritis multiplex). Necrotizing vasculitis was eventually confirmed by peripheral nerve biopsy. Biological markers of inflammation or eosinophilia were present in 5/8 and a progressive motor deficit (7/8) is suggestive of the diagnosis. Under steroid treatment, all patients improved during a mean of 2 years 6 months of follow-up (Mean Rankin score improvement 1.9 point), but five relapsed including three mononeuritis multiplex, and one had acral necrosis. Vasculitis presenting as LL radiculopathy is rare; EMG studies with signs of mononeuritis multiplex and nerve biopsy studies are useful for making the diagnosis.

Rodier, M.-H., El Moudni, B., Ghazali, M., Lacroix, C., and Jacquemin, J.-L. 1994. Electrophoretic detection of cytoplasmic serine proteinases (gelatinases) in Candida albicans. Experimental Mycology 18: 267-270. Proteolytic activities of Candida albicans were identified using sodium dodecyl sulfate-polyacrylamide gel electrophoresis with gels containing gelatin as proteinase substrate. Cytoplasmic extracts of five isolates were tested with this method. Two major proteolytic activities of Mr 50,000 and 60,000 were conserved between isolates whereas two other less intense activities of Mr 90,000 and 120,000 were only detected in three isolates. The two bands of proteolysis of Mr, 50,000 and 60,000 were revealed between pH 5.0 and pH 8.0, optimally active at pH 7.0, and their isoelectric point was 4.5. They were not influenced by the presence of 2-mercaptoethanol. Their sensitivity to phenylmethylsulfonyl fluoride and chymostatin allowed them to be characterized as serine proteinases. These two neutral proteinases were not secreted in culture supernatant.

Domino transplantation using the liver (DLT) from patient with familial amyloid polyneuropathy (FAP) has been developed to alleviate the graft shortage. We herein studied 91 patients who ...

Paragangliomas are tumors arising in the paraganglia. Involvement of the spine is less common, and usually takes the form of intradural compression of the cauda equina. We report here a case of a 60-year-old man with recurrent and progressive pain of his sacral and perineal area, accompanied by occasional rod and perineal hypoesthesia on admission. He underwent laminectomies of the vertebral bodies S1 and S2, and an en bloc resection of the tumor. Postoperative histopathological examination revealed a paraganglioma. Postoperative staging showed no pathological abnormalities, and no tumor recurrence after one year. Even though rare, the paraganglioma of the sacral spinal canal should be considered in the differential diagnosis of tumors occurring in the spine.