Diagnostic usefulness of plexus magnetic resonance imaging in chronic inflammatory demyelinating polyradiculopathy without electrodiagnostic criteria of demyelination.

BACKGROUND AND PURPOSE: The usefulness of plexus magnetic resonance imaging (MRI) in the diagnosis of chronic inflammatory demyelinating polyradiculopathy (CIDP) without definite European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria is currently unclear. METHODS: Data from consecutive patients with clinical manifestations suggesting CIDP, with or without (CIDP-D and CIDP-ND, respectively) definite EFNS/PNS electrodiagnostic criteria, and referred for plexus MRI in our imaging centre were retrospectively analysed. An expert committee of neurologists compared the level of suspicion of CIDP in CIDP-ND patients to the blinded/unblinded MRI findings. Plexus MRI was reviewed by a neuroradiologist blinded to the final diagnosis. RESULTS: In all, 38 patients were assessed with suspected CIDP-ND [7/38 (18%) probable; 13/38 (34%) possible; 18/38 (47%), no EFNS/PNS electrodiagnostic criteria], plus 10 with CIDP-D. Thirty-six of the 38 (95%) fulfilled clinical criteria of CIDP variants, including pure sensory neuropathy in 22/36 (61%). Plexus MRI showed abnormalities in 22/38 (58%) patients including increased nerve signal intensity on T2-weighted images in 22/22 (100%), nerve enlargement in 20/22 (91%) and contrast enhancement in 8/22 (36%). Plexus MRI enabled the expert committee's final diagnosis to be adjusted in 7/38 (18%) patients, and in conjunction with nerve conduction studies was a supportive criterion to classify 7/24 (29%) patients as definite CIDP. MRI abnormalities were more asymmetrical (P = 0.03) and less diffuse (P = 0.1) in CIDP-ND than in CIDP-D. CONCLUSIONS: Our observations suggest that plexus MRI makes a valuable contribution to the diagnosis of CIDP-ND patients. Further studies are needed to investigate inter-rater reliability of clinical and imaging criteria of CIDP in these patients, and the impact on outcomes.

High dose subcutaneous immunoglobulin for idiopathic inflammatory myopathies and dysimmune peripheral chronic neuropathies treatment: observational study of quality of life and tolerance.

BACKGROUND: In patients with autoimmune diseases who still derive benefit from high dose intravenous immunoglobulin (IVIg) treatment, some physicians resort to subcutaneous (SC) Ig as a replacement therapy. OBJECTIVE: To collect quality of life (QoL) and tolerance data on SCIg in patients for whom the switch from IVIg to SCIg is essential to maintain treatment. METHODS: This observational study included patients with either idiopathic inflammatory myopathies (IIM) or chronic dysimmune peripheral neuropathies (CDPN) treated with IVIg, who had been switched to SCIg administration for at least three months. The main objective was to describe the impact of SCIg on QoL after six months, using the generic Short-Form 36 questionnaire (SF-36). The secondary objectives were to evaluate SCIg tolerance and clinical efficiency. RESULTS: Eight centres recruited 12 IIM patients and two centres recruited 11 CDPN patients. Neither the physical nor the mental health SF-36 component summaries showed any QoL deterioration during the six-month study period and all IIM and CDPN patients remained clinically stable during the same period. The most frequent adverse effects were injection site reactions (50%), cutaneous tissue disorders (18.2%), and nervous system disorders (13.6%). Two serious adverse events (myocarditis and cerebrovascular accident) occurred in two patients. CONCLUSION: In these rare inflammatory diseases, high dose SCIg administration (which can be home based) has no deleterious effect on patient QoL. It appears to be a safe and efficient alternative to hospital-based IVIg.

[American Academy of Neurology, Washington, 18-25 April 2015]. / American Academy of Neurology, Washington, 18-25 avril 2015.

CEREBROVASCULAR DISEASES: The benefit of the thrombectomy using stents retrievers in the acute stroke phase is now demonstrated when there is a proximal occlusion of an intracranial artery, whatever its mechanism. The place of the anticoagulants in the management of cervical artery dissections remains uncertain, while the benefit of the blood pressure control in the secondary prevention of deep and lobar intracerebral hemorrhages is critical. The development of cardiac MRI, prolonged cardiac monitoring and transcranial doppler seems to improve the diagnosis of cardio-embolic sources of stroke. EPILEPSY: A specialized urgent-access single seizure clinic represents a model which reduces wait-times and improves patient access after a first fit. Co-locating a psychiatrist within outpatient epilepsy center leads to a reduction in psychiatric symptoms and people with psychogenic non-epileptic seizures. When neurologists around the world assess identical case scenarios for the diagnosis of epilepsy, concordance is between moderate and poor, showing that epilepsy diagnosis remains difficult. More than one third of elderly with new-onset epilepsy of unknown etiology exhibit temporal lobe atrophy on brain imaging. MOVEMENT DISORDERS: There is no major progress in the therapeutic approach of Parkinson's disease but the discovery of new genetic markers such as glucocerebrosidase mutations may greatly change our knowledge of the disease process and may induce new therapeutic strategies in the future. The natural history of the disease is also better understood from the prodromal phase to the post-mortem analysis of the brain and the classification of the processes based on abnormal protein deposits. DEMENTIA: The respective value of biomarkers (amyloid imaging versus CSF biomarkers) for in vivo diagnosis of Alzheimer's disease (AD) has been detailed. Therapeutic expectations mainly rely on anti-Aß immunization trials performed in preclinical (and no longer prodromal) stages of AD, with the aim of slowing the evolution of neuronal loss. Besides a lot of communications on dementia genetics or physiopathogeny, fascinating and promising results were presented on deep brain stimulation for depression resistant to medical treatment. PERIPHERAL NEUROPATHY: Ibudilast, administered with riluzole, is safe and tolerable in patients with amyotrophic lateral sclerosis (ALS), improves ALS function and delays progression. Patients with painful small fiber neuropathy have a high rate of mutations in the SCN9A gene, coding for Nav1.7 voltage-gated sodium-channels. Peripheral nerve lymphoma (NL) is a multifocal painful neuropathy that causes endoneurial inflammatory demyelination: primary NL is less severe than secondary NL, which occurs after remission, suggesting that nerve may be considered a "safe lymphoma haven". MULTIPLE SCLEROSIS (MS): Biotin in progressive forms of MS and daclizumab in relapsing-remitting forms appear to be promising treatments. In case of failure of current first-line and/or second-line therapeutics, alemtuzumab may be an interesting alternative treatment. Teriflunomide, dimethyl fumarate and fingolimod are oral treatments with confirmed efficacy and acceptable safety. Besides vitamin D insufficiency and smoking, which are confirmed risk factors for the disease, testosterone insufficiency (in males) and obesity are emerging risk factors, which could also be corrected.

Challenges in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare disease, the most frequent one within the spectrum of the so-called "chronic immune-mediated neuropathies". Challenges in the treatment of CIDP firstly concern its diagnosis, which may be difficult, mainly for the atypical forms. Secondly, challenges encompass the choice of the first-line treatment, such as corticosteroids, intravenous immunoglobulins (IVIg), and plasma exchanges (PE) that have been proven as efficacious by several randomized controlled trials (RCT). Recent reports have focused on both different regimens of corticosteroids, and the occurrence of relapses following treatment with either corticosteroids or IVIg. These data may be helpful for the choice of the first-line treatment and may result in changing the guidelines for treatment of CIDP in clinical practice. The third and more difficult challenge is to manage long-term treatment for CIDP, since no immunomodulatory treatment has to date been proven as efficacious in this situation. Lastly, challenges in the treatment concern the choice of the best outcome measure for CIDP in RCT and clinical practice. The aim of this article is to overview the results of the more recently reported published trials for CIDP, and to give some insights for the current and future management of CIDP.

Non-anti-MAG DADS neuropathy as a variant of CIDP: clinical, electrophysiological, laboratory features and response to treatment in 10 cases.

BACKGROUND AND PURPOSE: Some patients within the spectrum of chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) have distal acquired demyelinating symmetric (DADS) neuropathy, usually associated with anti-myelin-associated-glycoprotein (MAG) IgM monoclonal gammopathy. The aim of this retrospective study was to investigate patients with DADS neuropathy without anti-MAG antibodies, and study their response to immunotherapy. METHODS: Patients were selected on the basis of (i) 'Definite CIDP' according to the EFNS/PNS Guideline criteria, (ii) The presence of disproportionately prolonged motor latencies resulting in a terminal latency index (TLI) ≤ 0.25 in at least two motor nerves and (iii) The absence of anti-MAG antibodies on ELISA. Response to immunotherapy was defined as persistent improvement by at least one point on the INCAT disability score. RESULTS: Data from 146 CIDP patients were analysed, and 10 patients were included. Six had clinically pure sensory neuropathy, and four had sensorimotor neuropathy. Ataxia was present in nine patients, generalized areflexia in seven and postural tremor in two. Five of the 10 patients had abnormal sensory potentials only in the upper limbs. An associated condition was found in nine patients: two chronic lymphocytic leukaemias, four IgG monoclonal gammopathies (one associated with non-Hodgkin's lymphoma) and two IgM monoclonal gammopathies of unknown significance. Patients were mostly improved with intravenous immunoglobulin (IVIg), corticosteroids, plasma exchanges, or a combination thereof. CONCLUSION: DADS neuropathy without anti-MAG antibodies is more likely to be considered a variant of CIDP. In addition, such patients should be systematically investigated for an associated haematological or immunological condition.

A 4He vector zero-field optically pumped magnetometer operated in the Earth-field.

Low intrinsic noise, high bandwidth, and high accuracy vector magnetometers are key components for many ground or space geophysical applications. Here, we report the design and the test of a 4He vector optically pumped magnetometer specifically dedicated to these needs. It is based on a parametric resonance magnetometer architecture operated in the Earth magnetic field with closed-loop compensation of the three components of the magnetic field. It provides offset-free vector measurements in a ±70 µT range with a DC to 1 kHz bandwidth. We demonstrate a vector sensitivity up to 130 fT/√Hz, which is about ten times better than the best available fluxgate magnetometers currently available for the same targeted applications.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society.

BACKGROUND: Revision of the guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, published in 2005, has become appropriate owing to publication of more relevant articles. Most of the new studies focused on small fiber neuropathy (SFN), a subtype of neuropathy for which the diagnosis was first developed through skin biopsy examination. This revision focuses on the use of this technique to diagnose SFN. METHODS: Task force members searched the Medline database from 2005, the year of the publication of the first EFNS guideline, to June 30th, 2009. All pertinent articles were rated according to the EFNS and PNS guidance. After a consensus meeting, the task force members created a manuscript that was subsequently revised by two experts (JML and JVS) in the field of peripheral neuropathy and clinical neurophysiology, who were not previously involved in the use of skin biopsy. RESULTS AND CONCLUSIONS: Distal leg skin biopsy with quantification of the linear density of intraepidermal nerve fibers (IENF), using generally agreed upon counting rules, is a reliable and efficient technique to assess the diagnosis of SFN (Recommendation Level A). Normative reference values are available for bright-field immunohistochemistry (Recommendation Level A) but not yet for confocal immunofluorescence or the blister technique. The morphometric analysis of IENF density, either performed with bright-field or immunofluorescence microscopy, should always refer to normative values matched for age (Recommendation Level A). Newly established laboratories should undergo adequate training in a well-established skin biopsy laboratory and provide their own stratified for age and gender normative values, intra- and interobserver reliability, and interlaboratory agreement. Quality control of the procedure at all levels is mandatory (Good Practice Point). Procedures to quantify subepidermal nerve fibers and autonomic innervated structures, including erector pili muscles, and skin vessels, are under development but need to be confirmed by further studies. Sweat gland innervation can be examined using an unbiased stereologic technique recently proposed (Recommendation Level B). A reduced IENF density is associated with the risk of developing neuropathic pain (Recommendation Level B), but it does not correlate with its intensity. Serial skin biopsies might be useful for detecting early changes of IENF density, which predict the progression of neuropathy, and to assess degeneration and regeneration of IENF (Recommendation Level C). However, further studies are warranted to confirm its potential usefulness as an outcome measure in clinical practice and research. Skin biopsy has not so far been useful for identifying the etiology of SFN. Finally, we emphasize that 3-mm skin biopsy at the ankle is a safe procedure based on the experience of 10 laboratories reporting absence of serious side effects in approximately 35,000 biopsies and a mere 0.19% incidence of non-serious side effects in about 15 years of practice (Good Practice Point).

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision.

BACKGROUND: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System. OBJECTIVES: To revise these guidelines. METHODS: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion. RECOMMENDATIONS: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (i) intravenous immunoglobulin (IVIg) (Recommendation Level A) or corticosteroids (Recommendation Level C) should be considered in sensory and motor CIDP; (ii) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (iii) if IVIg and corticosteroids are ineffective, plasma exchange (PE) should be considered (Recommendation Level A); (iv) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (v) symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

[Cryoglobulinemic peripheral neuropathy in hepatitis C virus infection: clinical and anatomical correlations of 22 cases]. / Corrélations anatomocliniques des neuropathies périphériques cryoglobulinémiques secondaires à l'hépatite C. Série consécutive de 22 cas.

INTRODUCTION: Cryoglobulinemic neuropathies caused by hepatitis C virus are frequent and may have severe clinical outcomes. The aim of this study was to clarify the clinical and anatomical correlations of these neuropathies. METHODS: Between 1992 and 2007, 22 consecutive patients with cryoglobulinemic neuropathies caused by hepatitis C virus were retrospectively included. Patients were evaluated clinically, electrophysiologically and underwent a neuromuscular biopsy. The group of patients with vasculitis on nerve biopsy was compared with the group without vasculitis. RESULTS: All the neuropathies were axonal with 11 polyneuropathies and 11 mononeuropathies multiplex. The seven patients with medium-sized vasculitis on the nerve biopsy presented an acute sensorimotor mononeuropathy multiplex in six cases (85%), with ischemic conduction block in three cases (42%) and wallerian degeneration in four cases (57%). Among the four patients with small-sized vasculitis, two had a mononeuropathy multiplex (50%) without conduction block (0%) and with wallerian degeneration in one case (25%). The 11 patients without vasculitis (nine lymphocytic perivascular infiltrates and two non inflammatory biopsies) had a polyneuropathy in eight cases (72%) without conduction block and wallerian degeneration (0%). The type of neuropathy was different in the group of patients with vasculitis compared with the group without vasculitis. The neuropathies with vasculitis were significantly different with more frequent mononeuropathies multiplex (p<0.05), acute early stage (p<0.01), disability (p<0.05) and wallerian degeneration (p=0.01). CONCLUSION: Among hepatitis C patients with cryoglobulinemia, neuropathies with small-sized vasculitis show a pattern between severe mononeuropathies multiplex with medium-sized vasculitis and moderate polyneuropathies with lymphocytic perivascular infiltrates. In cryoglobulinemic vasculitis with hepatitis C, the severity of the neuropathy depends on the nature of the cellular inflammation and the size of the vessel involvement.

Native versus deglycosylated IgM in anti-MAG neuropathy: Correlation with clinical status - Study of 10 cases.

BACKGROUND/PURPOSE: In anti-myelin associated glycoprotein (anti-MAG) neuropathies, there is evidence that anti-MAG antibodies are pathogenic but numerous studies report the absence or a weak correlation between the titers of these antibodies and disease course. In this study we assessed the relationships between MAG and glycosylated moieties located on Fc fragment of IgM anti-MAG. MATERIAL AND METHODS: IgM were extracted from the serum of 8 patients with anti-MAG neuropathy and in 2 patients with anti-MAG antibodies without anti-MAG neuropathy. Anti-MAG activity was performed with pre- and post-deglycosylated IgM extracts using indirect immunofluorescence (IIF) and ELISA. Sera from 49 patients with IgM monoclonal gammopathy without neurological disease were tested as control group (CG). Results were compared to clinical scores. For 4 patients the affinity constant of IgM with MAG was analyzed pre- and post-deglycosylated, using surface plasmon resonance technology (SPR). RESULTS: The relationships between MAG and glycosylated moieties of IgM anti-MAG were confirmed by kinetic and immunological assays. Deglycosylation resulted in a decrease in anti-MAG titers. Post-deglycosylation anti-MAG titers trended with changes in IgM titers and allowed quantifying anti-MAG antibodies without a saturation of the testing method. After deglycosylation, the titers better represented pathogenic activity and help to follow a given patient's clinical status prospectively. Six patients from CG (12.2%) had anti-MAG antibody titers over positive threshold: 1000 Bühlmann-Titer-Units (BTU) supporting the hypothesis of neutral intermolecular interactions between IgM and MAG. Deglycosylation allowed distinguishing infra clinical forms from neutral relationships forms, when the titers are weak but this assay remains essentially a diagnostic tool.

[Multifocal motor neuropathy: a retrospective study of sensory nerve conduction velocities in long-term follow-up of 21 patients]. / Neuropathie motrice multifocale: existe-t-il une altération de la conduction sensitive au long cours? Une étude rétrospective chez 21 patients.

INTRODUCTION: Multifocal motor neuropathy is a well described condition characterized by slowly progressive, predominantly distal, asymmetric limb weakness and wasting, predominantly in the arms within an anatomical distribution of individual motor nerves, with minimal or no sensory involvement. METHOD: The aim of this retrospective study was to look for a significant reduction of the amplitude of sensory potentials in a cohort of 21 patients with defined multifocal motor neuropathy according to the Workshop Report criteria [Workshop Report, 2001. 79th ENMC International Workshop. Multifocal motor neuropathy 14-15 April 2000, Hilversum. The Netherlands. Muscle Nerve 11, 309-314], within a follow-up of at least 3 years. RESULT: Thirteen patients (62%) (Group 1) had a reduction of the amplitude of at least one sensory potential, of whom four patients had abnormalities of two or more sensory potentials, while eight patients (Group 2) had no abnormality. No significant differences were found for gender, age at onset, number of involved motor nerves, CSF protein count, presence/absence of anti-GM1 serum antibodies and response to IgIV between the two groups. CONCLUSION: This study underlines the difficulty in defining criteria for multifocal motor neuropathies capable of distinguishing them from other chronic acquired demyelinating polyneuropathies, and mainly from multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, also called Lewis-Sumner's syndrome.

Intravenous immunoglobulin as short- and long-term therapy of multifocal motor neuropathy: a retrospective study of response to IVIg and of its predictive criteria in 40 patients.

OBJECTIVE: To document short-term and long-term responses to a single type of intravenous immunoglobulin (IVIg) in a large cohort of patients with multifocal motor neuropathy (MMN). METHODS: A retrospective study was conducted in 40 patients with MMN included on ENMC Workshop criteria, and treated with periodic IVIg infusions between 1995 and 2003. The short-term response was defined as improvement of at least 1 point on the MRC score in at least two affected muscles at 6 months. The population comprised 22 treatment-naïve patients (who had never received IVIg before inclusion), and 18 previously treated patients. For the long-term evaluation (>6 months), the patients were classified into three groups according to the dependency or not on periodic IVIg. In addition, changes in conduction block (CB) and predictive criteria for response to IVIg were explored. RESULTS: The MRC score significantly improved (p<0.0001) in 14 (70%; 95% CI 0.46 to 0.88) of the 20 treatment-naïve patients (missing data for 2 patients). None of the predictive criteria studied were found to be significant. At the end of follow-up (mean of 2.2+/-2.0 years), only 8 of the 40 patients (22%) had significant remission, whereas 25 patients (68%) were dependent on periodic IVIg infusions. The number of CBs decreased or remained unchanged in 12 treatment-naïve patients and increased in 2 such patients. CONCLUSIONS: This study confirmed a significantly high short-term response to IVIg of patients with MMN, but showed contrasted results in long-term follow-up. No predictive factors for response to IVIg were found.

Neuropathy in lymphoma: a relationship between the pattern of neuropathy, type of lymphoma and prognosis?

BACKGROUND: Neuropathies associated with lymphoma (NAL) are rare and present a great clinical heterogeneity, making them difficult to diagnose and worsening their prognosis. OBJECTIVES: (1) To report the different patterns of NAL and discuss the mechanisms encountered; (2) to determine the relationship between a given type of lymphoma and a specific type of neuropathy; and (3) to assess the prognosis of NAL. METHODS: Among 150 patients with lymphoma and neuropathy, we selected 26 in whom the neuropathy was not related to drug induced or IgM-antimyelin associated glycoprotein neuropathies. The pattern of neuropathy was defined in terms of its clinical and electrophysiological features. Neurological improvement, haematological remission and occurrence of death were taken into account to determine the prognosis. RESULTS: 13 patients (50%) had a demyelinating polyneuropathy (PNP), seven (27%) had a radiculopathy linked to proximal root tumoral infiltration and six (23%) had an axonal multiple mononeuropathy (MM) related to distal lymphomatous infiltration or to paraneoplastic microvasculitis. Hodgkin's lymphoma was only associated with demyelinating PNP. High grade B cell lymphoma was strongly associated with radiculopathy. Neurological improvement was observed in 69% of patients with demyelinating PNP, 29% with radiculopathy and 50% with MM. Haematological remission was observed in 46% of patients with demyelinating PNP, 29% with radiculopathy and 83% with MM. CONCLUSIONS: Demyelinating PNP, the most frequently observed neuropathy in this study, had the best neurological prognosis. Chemotherapy combined with immune mediated treatment was the most effective treatment in this group. Identifying the type and mechanism of NAL is crucial in order to define the therapeutic strategy and improve the prognosis.