Hereditary transthyretin amyloidosis in middle-aged and elderly patients with idiopathic polyneuropathy: a nationwide prospective study.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is an adult-onset autosomal dominant disease resulting from TTR gene pathogenic variants. ATTRv often presents as a progressive polyneuropathy, and effective ATTRv treatments are available. METHODS: In this 5 year-long (2017-2021) nationwide prospective study, we systematically analysed the TTR gene in French patients with age >50 years with a progressive idiopathic polyneuropathy. RESULTS: 553 patients (70% males) with a mean age of 70 years were included. A TTR gene pathogenic variant was found in 15 patients (2.7%), including the Val30Met TTR variation in 10 cases. In comparison with patients with no TTR gene pathogenic variants (n = 538), patients with TTR pathogenic variants more often presented with orthostatic hypotension (53 vs. 21%, p = .007), significant weight loss (33 vs 11%, p = .024) and rapidly deteriorating nerve conduction studies (26 vs. 8%, p = .03). ATTRv diagnosis led to amyloid cardiomyopathy diagnosis in 11 cases, ATTRv specific treatment in all cases and identification of 15 additional ATTRv cases among relatives. CONCLUSION: In this nationwide prospective study, we found ATTRv in 2.7% of patients with age >50 years with a progressive polyneuropathy. These results are highly important for the early identification of patients in need of disease-modifying treatments.

Investigation and Management of Immunoglobulin M- and Waldenström-Associated Peripheral Neuropathies.

The immunoglobulin M (IgM)-associated peripheral neuropathies (PN) are a heterogeneous group of disorders representing most paraproteinemic neuropathy cases. They are associated with IgM monoclonal gammopathy of undetermined significance (MGUS) or Waldenström macroglobulinemia. Establishing a causal link between a paraprotein and neuropathy can be challenging but is necessary to adopt an appropriate therapeutic approach. The most common type of IgM-PN is Antimyelin-Associated-Glycoprotein neuropathy, but half of the cases are of other causes. Progressive functional impairment is an indication for treatment, even when the underlying disorder is IgM MGUS, involving either rituximab monotherapy or combination chemotherapy to achieve clinical stabilization.

Neurolymphomatosis: involvement of peripheral nervous system revealing hematologic malignancy, a report of nine cases.

BACKGROUND AND AIM: Neurolymphomatosis is defined as an infiltration of the peripheral nervous system (PNS) by malignant lymphoma cells. It is a rare entity and diagnosis is complicated especially when PNS involvement is the initial and leading symptom. To improve knowledge of the disorder and shorten the time to diagnosis, we report a series of nine patients without a history of hematologic malignancy, who were diagnosed with neurolymphomatosis after evaluation and workup of peripheral neuropathy. METHODS: The patients were included from the Department of Clinical Neurophysiology at Pitié Salpêtrière and Nancy Hospitals over a period of 15 years. Diagnosis of neurolymphomatosis was confirmed by histopathologic examination for each patient. We characterized their clinical, electrophysiological, biological, imaging, and histopathologic features. RESULTS: The neuropathy was characterized by pain (78%), proximal involvement (44%) or of all four limbs (67%), asymmetrical or with multifocal distribution (78%), abundant fibrillation (78%), a tendency to worsen rapidly, and significant associated weight loss (67%). Neurolymphomatosis was diagnosed principally on nerve biopsy (89%) identifying infiltration of lymphoid cells, atypical cells (78%), a monoclonal population (78%), and supported by fluorodeoxyglucose-positron emission tomography, spine or plexus MRI, cerebrospinal fluid analysis, and blood lymphocyte immunophenotyping. Six patients had systemic disease and three impairment limited to the PNS. In the latter case, progression could be unpredictable and may be diffuse and explosive, sometimes occurring years after a seemingly indolent course. INTERPRETATION: This study provides better knowledge and understanding of neurolymphomatosis when neuropathy is the initial presentation.

Anti-disialosyl-immunoglobulin M chronic autoimmune neuropathies: a nationwide multicenter retrospective study.

BACKGROUND AND PURPOSE: In this retrospective study involving 14 university hospitals from France and Switzerland, the aim was to define the clinicopathological features of chronic neuropathies with anti-disialosyl ganglioside immunoglobulin M (IgM) antibodies (CNDA). RESULTS: Fifty-five patients with a polyneuropathy evolving for more than 2 months and with at least one anti-disialosyl ganglioside IgM antibody, that is, anti-GD1b, -GT1b, -GQ1b, -GT1a, -GD2 and -GD3, were identified. Seventy-eight percent of patients were male, mean age at disease onset was 55 years (30-76) and disease onset was progressive (82%) or acute (18%). Patients presented with limb sensory symptoms (94% of cases), sensory ataxia (85%), oculomotor weakness (36%), limb motor symptoms (31%) and bulbar muscle weakness (18%). Sixty-five percent of patients had a demyelinating polyradiculoneuropathy electrodiagnostic profile and 24% a sensory neuronopathy profile. Anti-GD1b antibodies were found in 78% of cases, whilst other anti-disialosyl antibodies were each observed in less than 51% of patients. Other features included nerve biopsy demyelination (100% of cases), increased cerebrospinal fluid protein content (75%), IgM paraprotein (50%) and malignant hemopathy (8%). Eighty-six percent of CNDA patients were intravenous immunoglobulins-responsive, and rituximab was successfully used as second-line treatment in 50% of cases. Fifteen percent of patients had mild symptoms and were not treated. CNDA course was progressive (55%) or relapsing (45%), and 93% of patients still walked after a mean disease duration of 11 years. CONCLUSION: Chronic neuropathies with anti-disialosyl ganglioside IgM antibodies have a recognizable phenotype, are mostly intravenous immunoglobulins-responsive and present with a good outcome in a majority of cases.

Immunochemotherapy versus rituximab in anti-myelin-associated glycoprotein neuropathy: A report of 64 patients.

Monoclonal immunoglobulin M (IgM) anti-myelin-associated glycoprotein (MAG) neuropathy is a rare disabling condition, most commonly treated with rituximab monotherapy (R), which leads to neurological improvement in only 30%-50% of patients. The combination of rituximab plus chemotherapy has been proven to improve the level of responses. We studied the outcomes of anti-MAG neuropathy patients treated either by R, or by immunochemotherapy (ICT) in our centre, focusing on the incidence of the first neurological response evaluated by the modified Rankin scale (mRS). From 2011 to 2018, 64 patients were studied: 34 were treated with R and 30 with ICT. According to our treatment decision-making process, the median mRS was higher in the ICT group (mRS 2) than in the R group (mRS 1). At one year, improvements of the mRS rates were 46% and 18% in the ICT and R groups of patients respectively, with median times to response of eight and 13 months (p = 0.023). Adverse effects were higher in the ICT group: 62% vs 15% (p Ë‚ 0.01), all grades included. One secondary acute leukaemia occurred five years after treatment with ICT. In conclusion, ICT may be used as a valid option for patients with rapidly progressive and/or severe anti-MAG neuropathy symptoms.

Motor neuron pathology in CANVAS due to RFC1 expansions.

CANVAS caused by RFC1 biallelic expansions is a major cause of inherited sensory neuronopathy. Detection of RFC1 expansion is challenging and CANVAS can be associated with atypical features. We clinically and genetically characterized 50 patients, selected based on the presence of sensory neuronopathy confirmed by EMG. We screened RFC1 expansion by PCR, repeat-primed PCR, and Southern blotting of long-range PCR products, a newly developed method. Neuropathological characterization was performed on the brain and spinal cord of one patient. Most patients (88%) carried a biallelic (AAGGG)n expansion in RFC1. In addition to the core CANVAS phenotype (sensory neuronopathy, cerebellar syndrome and vestibular impairment), we observed chronic cough (97%), oculomotor signs (85%), motor neuron involvement (55%), dysautonomia (50%), and parkinsonism (10%). Motor neuron involvement was found for 24 of 38 patients (63.1%). First motor neuron signs, such as brisk reflexes, extensor plantar responses, and/or spasticity, were present in 29% of patients, second motor neuron signs, such as fasciculations, wasting, weakness, or a neurogenic pattern on EMG in 18%, and both in 16%. Mixed motor and sensory neuronopathy was observed in 19% of patients. Among six non-RFC1 patients, one carried a heterozygous AAGGG expansion and a pathogenic variant in GRM1. Neuropathological examination of one RFC1 patient with an enriched phenotype, including parkinsonism, dysautonomia, and cognitive decline, showed posterior column and lumbar posterior root atrophy. Degeneration of the vestibulospinal and spinocerebellar tracts was mild. We observed marked astrocytic gliosis and axonal swelling of the synapse between first and second motor neurons in the anterior horn at the lumbar level. The cerebellum showed mild depletion of Purkinje cells, with empty baskets, torpedoes, and astrogliosis characterized by a disorganization of the Bergmann's radial glia. We found neuronal loss in the vagal nucleus. The pars compacta of the substantia nigra was depleted, with widespread Lewy bodies in the locus coeruleus, substantia nigra, hippocampus, entorhinal cortex, and amygdala. We propose new guidelines for the screening of RFC1 expansion, considering different expansion motifs. Here, we developed a new method to more easily detect pathogenic RFC1 expansions. We report frequent motor neuron involvement and different neuronopathy subtypes. Parkinsonism was more prevalent in this cohort than in the general population, 10% versus the expected 1% (P < 0.001). We describe, for the first time, the spinal cord pathology in CANVAS, showing the alteration of posterior columns and roots, astrocytic gliosis and axonal swelling, suggesting motor neuron synaptic dysfunction.

Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy.

Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.

Focal chronic inflammatory demyelinating polyradiculoneuropathy: Onset, course, and distinct features.

Focal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is defined as involving the brachial or lumbosacral plexus, or one or more peripheral nerves in one upper or one lower limb (monomelic distribution). However, other auto-immune neuropathies such as Lewis-Sumner syndrome (LSS) and multifocal motor neuropathy (MMN) can also have a focal onset. From a retrospective cohort of 30 focal CIDP patients with a monomelic onset dating back at least 2 years, we distinguished patients with plexus involvement (focal demyelinating plexus neuropathy [F-PN], n = 18) from those with sensory or sensorimotor (F-SMN, n = 7), or purely motor (F-MN, n = 5) impairment located in one or several peripheral nerves. Few (39%) F-PN patients had motor nerve conduction abnormalities, but the majority showed proximal conduction abnormalities in somatosensory evoked potentials (80%), and all had focal hypertrophy and/or increased short tau inversion recovery image signal intensity on plexus MRI. Impairment remained monomelic in most (94%) F-PN patients, whereas abnormalities developed in other limbs in 57% of F-SMN, and 40% of F-MN patients (P = .015). The prognosis of F-PN patients was significantly better: none had an ONLS score > 2 at the final follow-up visit, vs 43% of F-SMN patients and 40% of F-MN patients (P = .026). Our findings from a large cohort of focal CIDP patients confirm the existence of different entities that are typically categorized under this one term: on the one hand, patients with a focal plexus neuropathy and on the other, patients with monomelic sensori-motor or motor involvement of peripheral nerves. These two last subgroups appeared to be more likely to evolve to LSS or MMN phenotype, when F-PN patients have a more distinctive long-term, focal, benign course.

Confirmed cases of Neuroborreliosis with involvement of peripheral nervous system: Description of a cohort.

The manifestations of borreliosis in the peripheral nervous system (PNS) remain poorly described. As the symptoms of neuroborreliosis can be reversed with timely introduction of antibiotics, early identification could avoid unnecessary axonal loss. Our aim was to describe the characteristics of confirmed neuroborreliosis cases involving the PNS diagnosed between 2007 and 2017 in our neuromuscular disease center in a nonendemic area (La Pitié-Salpêtrière Hospital, Paris, France).Neuroborreliosis was defined as follows: compatible neurological symptoms without other cause of neuropathy; cerebrospinal fluid and serum analysis (positive serological tests with ELISA, confirmed by Western Blot); and improvement of symptoms with adapted antibiotherapy. All the patients consulting in our center between 2007 and 2017 underwent electrophysiological study.Sixteen confirmed cases of neuroborreliosis involving the PNS were included: 10 cases of meningoradiculoneuritis, 4 of axonal neuropathy, and 2 of demyelinating neuropathy (one acute and one chronic). Only 4 (25%) patients reported tick bites. Meningoradiculoneuritis was characterized by lymphocytic meningitis, intense pain, cranial nerve palsy, and contrast enhancement of nerve roots on imagery. The patients with axonal neuropathy presented sensory symptoms with intense pain but no motor deficit and meningitis was rare. Nerve biopsy of 1 patient revealed lymphocytic vasculitis. Electrophysiological testing showed sensory or sensorimotor axonal neuropathy (3 subacute and 1 chronic) of the lower limbs, with asymmetrical neuropathy in 1 patients, symmetrical neuropathy in one and monomelic sensory mononeuritis multiplex in another. We also found 1 case of acute demyelinating neuropathy, treated with antibiotherapy and immunoglobulins, and 1 chronic demyelinating neuropathy. Overall, diaphragmatic paralysis was frequent (18.6%). Antibiotherapy (mostly ceftriaxone 3-4 weeks) resulted in symptom resolution.This series gives an updated overview of the peripheral complications of neuroborreliosis to help identify this disease so that timely treatment could avoid axonal loss.

CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell-targeted therapies.

CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia; n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenström macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera.

INTRODUCTION: IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP. METHODS: 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department. RESULTS: IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies). CONCLUSIONS: Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) in 17 patients: Clinical characteristics, electrophysiological study, and response to treatment.

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and poorly described subtype of CIDP. We aimed to study their clinical and electrophysiological characteristics and response to treatment. From a prospective database of CIDP patients, we included patients with definite or probable CIDP with motor signs and without sensory signs/symptoms at diagnosis. Patients were considered to have pure motor CIDP (PM-CIDP) if sensory conductions were normal or to have motor predominant CIDP (MPred-CIDP) if ≥2 sensory nerve action potential amplitudes were abnormal. Among the 700 patients with CIDP, 17 (2%) were included (PM-CIDP n = 7, MPred-CIDP n = 10); 71% were male, median age at onset was 48 years (range: 13-76 years), 47% had an associated inflammatory or infectious disease or neoplasia. At the more severe disease stage, 94% of patients had upper and lower limb weakness, with distal and proximal weakness in 4 limbs for 56% of them. Three-quarters (75%) responded to intravenous immunoglobulins (IVIg) and four of five patients to corticosteroids including three of three patients with MPred-CIDP. The most frequent conduction abnormalities were conduction blocks (CB, 82%) and F-wave abnormalities (88%). During follow up, 4 of 10 MPred-CIDP patients developed mild sensory symptoms; none with PM-CIDP did so. Patients with PM-CIDP had poorer outcome (median ONLS: 4; range: 22-5) compared to MPred-CIDP (2, range: 0-4; P = .03) at last follow up. This study found a progressive clinical course in the majority of patients with motor CIDP as well as frequent associated diseases, CB, and F-wave abnormalities. Corticosteroids might be considered as a therapeutic option in resistant IVIg patients with MPred-CIDP.

Electrophysiological features of chronic inflammatory demyelinating polyradiculoneuropathy associated with IgG4 antibodies targeting neurofascin 155 or contactin 1 glycoproteins.

OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) with antibodies against neurofascin 155 (Nfasc155) or contactin-1 (CNTN1) have distinctive clinical features. Knowledge on their electrophysiological characteristics is still scarce. In this study, we are investigating whether these patients have specific electrophysiological characteristics. METHODS: The electrophysiological data from 13 patients with anti-Nfasc155 IgG4 antibodies, 9 with anti-CNTN1 IgG4 antibodies were compared with those of 40 consecutive CIDP patients without antibodies. RESULTS: All the patients with antibodies against Nfasc155 or CNTN1 fulfilled the EFNS/PNS electrodiagnostic criteria for definite CIDP. There was no electrophysiological difference between patients with anti-CNTN1 and anti-Nfasc155 antibodies. Nerve conduction abnormalities were heterogeneously distributed along nerves trunks and roots. They were more pronounced than in CIDP without antibodies. Motor conduction velocity on median nerve <24 m/s or motor velocity on ulnar nerve <26 m/s or motor distal latency on ulnar nerve >7.4 ms were predictive of positive antibodies against the node of Ranvier with a sensitivity of 59% and a specificity of 93%. CONCLUSIONS: Marked conduction abnormalities may suggest the presence of positive antibodies against the node of Ranvier. SIGNIFICANCE: Anti-Nfasc155 and anti-CNTN1 antibodies target the the paranodal axo-glial domain but are associated with nerve conduction abnormalities mimicking a "demyelinating" neuropathy.

Guillain-Barré Syndrome During Platinum-Based Chemotherapy: A Case Series and Review of the Literature.

Platinum-based chemotherapy is commonly associated with toxic sensory neuropathies, but also, although rarely, with Guillain-Barré syndrome (GBS). We describe five patients who developed GBS while receiving platinum-based chemotherapy for a solid tumor and report the five cases published so far. Most patients had received cumulative platinum doses below known neurotoxic levels, and all of them had an optimal outcome after platinum discontinuation, associated in most cases with administration of intravenous immunoglobulin. Clinical presentation, electroneuromyography, and cerebrospinal fluid analysis help clinicians to differentiate GBS from toxic neuropathy. Platinum compounds are the only chemotherapeutic agents used for solid tumors that have been associated to GBS. Thus, we propose that GBS may constitute a non-dose-dependent side effect of platinum drugs and that awareness needs to be raised among oncologists on this rare but potentially life-threatening complication of platinum chemotherapy. IMPLICATIONS FOR PRACTICE: Many patients on platinum-based chemotherapy for solid tumors develop sensory neuropathy, a common dose-dependent side effect. The authors propose that Guillain-Barré syndrome may constitute an immune-mediated, non-dose-related side effect of platinum-based chemotherapy. Prompt diagnosis of Guillain-Barré syndrome and distinction from classical toxic neuropathy are crucial for optimal treatment. Platinum discontinuation, associated if needed to intravenous immunoglobulin administration, radically changes the course of the disease and minimizes neurological sequelae.

Rituximab in chronic inflammatory demyelinating polyradiculoneuropathy with associated diseases.

We aimed to analyse the response to rituximab in a cohort of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients with associated disorders. We conducted a clinical and electrophysiological retrospective monocentric study in 28 CIDP patients. Response to rituximab was defined as (a) a five-point increase in the Medical Research Council sum score or a one-point decrease in the Overall Neuropathy Limitations Scale score, compared to the score at the first rituximab infusion, or (b) the discontinuation of, or reduced need for, the last treatments before rituximab initiation. Twenty-one patients (75%) were responders to rituximab. The median time before response was 6 months (1-10 months). Only two patients needed to be treated again during a median follow-up of 2.0 years (0.75-9 years). Interestingly, the response rate was good in patients with associated autoimmune disease (5/8) and similar to the response rate observed in patients with a haematological disease (16/20) (P = 0.63). A shorter disease duration was associated with a better clinical response to rituximab (odds ratio 0.81, P = 0.025) and the response rate was better (P = 0.05) in common forms (83.3%) than in sensory forms (42.9%). No major adverse events were recorded. Rituximab is efficacious in CIDP patients with haematological or autoimmune disease. It improves clinical response and decreases dependence on first-line treatments.

Pathology of Nerve Biopsy and Diagnostic Yield of PCR-Based Clonality Testing in Neurolymphomatosis.

Infiltration of the peripheral nervous system (PNS) by lymphoma, called neurolymphomatosis, is a rare condition among the spectrum of lymphoma-associated neuropathies; its diagnosis is challenging. Cerebrospinal fluid (CSF) analysis is of great value, but nerve biopsy (NB) may be necessary to prove invasion by malignant cells. Clonality polymerase chain reaction (PCR)-based analysis is a validated method in the diagnosis of hematological malignancies, but there are very little data on its diagnostic yield on NB samples. We explored the contribution of NB with clonality analysis to the diagnosis of neurolymphomatosis in 15 patients with negative CSF analysis. Moreover, we assessed the performance of clonality testing in a case-control manner, using patients with inflammatory infiltrates on NB as controls. Neurolymphomatosis was the first manifestation of lymphoma in 60% and could be diagnosed on routine histology alone in 40%. Clonality testing showed monoclonal rearrangement in 86.7% and was unsuccessful in 8.1%. Performance of clonality testing was as follows: 92.9% positive predictive value, 90% negative predictive value, 86.7% sensitivity, 94.7% specificity. This study confirms the diagnostic challenge of neurolymphomatosis, the usefulness of NB in patients with negative CSF analysis, and highlights the high yield of PCR-based clonality testing to assess the malignant nature of PNS lymphoid infiltrates.

Tremor Associated with Chronic Inflammatory Demyelinating Polyneuropathy and Anti-Neurofascin-155 Antibodies.

Background: Tremor is an underrecognized feature in certain neuropathy subtypes. Phenomenology shown: We show a patient with a disabling neuropathic tremor and mild cerebellar syndrome associated with chronic inflammatory demyelinating polyneuropathy (CIDP) and anti-neurofascin-155 (NF155) antibodies. Educational value: Anti-NF155 testing should be considered in patients with CIDP and disabling tremor because of therapeutic implications.