Serum neurofilament light and glial fibrillary acidic protein levels are not associated with wearing-off symptoms in natalizumab-treated multiple sclerosis patients.

Background: Biomarkers of neuronal and axonal damage (serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP)) may provide insight into the aetiology of natalizumab wearing-off symptoms (WoSs).

Objectives: We investigated the longitudinal association between and predictive value of sNfL and sGFAP and the occurrence of WoS in MS patients treated with natalizumab.

Methods: We performed longitudinal measurements of sNfL and sGFAP in NEXT-MS trial participants who completed a questionnaire about WoS.

Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial.

Background And Objectives: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID.

Methods: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4-7 weeks).

Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS).

Background: Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.

Methods: The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study.

The magnitude of neurotoxicity in patients with multiple myeloma and the impact of dose modifications: results from the population-based PROFILES registry.

The aim of this analysis is to assess (1) self-reported chemotherapy-induced peripheral neuropathy (CIPN) symptoms; (2) its association with sociodemographic and clinical characteristics; and (3) treatment dose modifications and its influence on the magnitude of neurotoxicity in a population-based cohort of patients with multiple myeloma (MM). MM patients (n = 156), diagnosed between 2000 and 2014, filled out the EORTC QLQ-CIPN20 (65% response). Data on treatment, outcomes, and dose modifications were extracted from the medical files.

Chemotherapy-induced neuropathy in multiple myeloma: influence on quality of life and development of a questionnaire to compose common toxicity criteria grading for use in daily clinical practice.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) may negatively influence multiple myeloma (MM) patients' health-related quality of life (HRQOL). Dose modification is the only way to minimize CIPN. To measure CIPN in daily practice, the Indication for Common Toxicity Criteria (CTC) Grading of Peripheral Neuropathy Questionnaire (ICPNQ) was developed which can be completed within five minutes by the patient.

[Concentration problem or epilepsy? Sudden changes in behaviour in adolescents].

Sudden changes in behaviour and concentration problems can be caused by non-convulsive status epilepticus. This generalised form of epilepsy can be easily missed as a diagnosis. In this case report series we describe three adolescent boys (13, 14 and 17 years old respectively) presenting with behavioural disturbances caused by idiopathic non-convulsive status epilepticus.

Prevalence, specificity and functionality of anti-ganglioside antibodies in neuropathy associated with IgM monoclonal gammopathy.

IgM antibodies against gangliosides and their complexes were studied in sera from 54 patients with polyneuropathy and IgM monoclonal gammopathy (IgM-PNP) without anti-MAG antibodies. Anti-ganglioside antibodies were found in 19 (35%) patients. Five (9%) patients had antibodies against ganglioside complexes.

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS).

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study.

Modifying the Medical Research Council grading system through Rasch analyses.

The Medical Research Council grading system has served through decades for the evaluation of muscle strength and has been recognized as a cardinal feature of daily neurological, rehabilitation and general medicine examination of patients, despite being respectfully criticized due to the unequal width of its response options. No study has systematically examined, through modern psychometric approach, whether physicians are able to properly use the Medical Research Council grades. The objectives of this study were: (i) to investigate physicians' ability to discriminate among the Medical Research Council categories in patients with different neuromuscular disorders and with various degrees of weakness through thresholds examination using Rasch analysis as a modern psychometric method; (ii) to examine possible factors influencing physicians' ability to apply the Medical Research Council categories through differential item function analyses; and (iii) to examine whether the widely used Medical Research Council 12 muscles sum score in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy would meet Rasch model's expectations.

Prognosis of polyneuropathy due to IgM monoclonal gammopathy: a prospective cohort study.

Background: The disease course of polyneuropathy associated with immunoglobulin M monoclonal gammopathy (IgM MGUSP) can be highly variable. In order to identify factors that influence long-term disease outcome, a prospective cohort study was performed of 140 patients with IgM MGUSP over a period of 23 years.

Methods: All patients with IgM MGUSP who were diagnosed in our tertiary referral center for polyneuropathy were eligible.

Detection of anti-MAG antibodies in polyneuropathy associated with IgM monoclonal gammopathy.

Background: Detection of serum antibodies to myelin-associated glycoprotein (MAG) by Western blot (WB) is a valuable assay to diagnose a distinct type of demyelinating polyneuropathy with immunoglobulin M (IgM) monoclonal gammopathy. In this study, the diagnostic accuracy of a new and more practical ELISA to detect these antibodies was validated.

Methods: Routine WBs from 2 independent laboratories and ELISA were used to detect anti-MAG IgM in serum from 207 patients with neuropathy and controls.

Rituximab for polyneuropathy with IgM monoclonal gammopathy.

Background: Polyneuropathy with IgM monoclonal gammopathy can be a disabling disorder necessitating treatment.

Methods: In a prospective open label trial, 17 patients with disabling IgM MGUS polyneuropathy were treated with rituximab, a chimeric anti-CD-20 monoclonal antibody.

Results: Rituximab induced an improvement of >or=1 point on the Overall Disability Sum Score in 2/17 patients, an improvement of >or=5% of the distal MRC sum score in 4/17 and the sensory sum score in 9/17 patients.

Intermittent cyclophosphamide with prednisone versus placebo for polyneuropathy with IgM monoclonal gammopathy.

Background: The best treatment for polyneuropathy associated with IgM monoclonal gammopathy (MGUS) is unknown. Oral cyclophosphamide combined with prednisone showed limited efficacy in a previous open label pilot study. We therefore performed a double-blind, randomized, placebo-controlled study of combined oral cyclophosphamide and prednisone in IgM MGUS polyneuropathy.

Cytogenetic aberrations in neuropathy associated with IgM monoclonal gammopathy.

The occurrence and nature of cytogenetic aberrations in polyneuropathy associated with IgM monoclonal gammopathy was determined. Therefore, interphase fluorescence in situ hybridization (FISH) was applied in 22 patients with polyneuropathy associated with IgM monoclonal gammopathy, multiplex ligation-dependent probe amplification (MLPA) assay in 18 of these patients and genome-wide-array-based comparative genomic hybridization (CGH) in eight of these 18 patients. Four patients had 10-20% and one patient had 30% B cells with IgH rearrangements; one patient had additional loss of 14qter; one patient had amplification of 6p and loss of 6q.

Neurologic and hematologic response to fludarabine treatment in IgM MGUS polyneuropathy.

We studied the efficacy of fludarabine in 16 patients with immunoglobulin M monoclonal gammopathy of unknown significance polyneuropathy in a prospective uncontrolled trial. The modified Rankin scale improved in 5/16 patients, all of whom had a demyelinating polyneuropathy. The motor conduction velocity improved by more than 10% in two or more nerves for four of five of these patients.

Immunoglobulin gene analysis in polyneuropathy associated with IgM monoclonal gammopathy.

Antineural antibody activity is the implicated pathogenic mechanism in polyneuropathy associated with monoclonal gammopathy. Recognition of antigen depends on immunoglobulin variable regions, encoded by V genes. We studied V(H)DJ(H) and V(L)J(L) gene use in monoclonal B cells by clonal analysis in 20 patients with polyneuropathy and IgM monoclonal gammopathy.

Malignant transformation in polyneuropathy associated with monoclonal gammopathy.

Objective: To assess the frequency of hematologic malignancies at diagnosis and to determine the incidence and predictors of malignant transformation during follow-up in patients with polyneuropathy associated with monoclonal gammopathy.

Methods: Potential predictors of malignant transformation from medical history, hematologic, neurologic, and laboratory examination performed each 6 months were evaluated by univariable and multivariable Cox proportional hazard analysis.

Results: Of 193 patients with polyneuropathy associated with monoclonal gammopathy, 17 patients had a hematologic malignancy at diagnosis.

G3139, a Bcl-2 antisense oligodeoxynucleotide, induces clinical responses in VAD refractory myeloma.

Expression of Bcl-2 in multiple myeloma is associated with resistance to chemotherapeutic drugs. Conversely, suppression of Bcl-2 enhanced the chemosensitivity of myeloma cells in vitro. G3139 is an antisense oligodeoxynucleotide targeted to the first six codons of the Bcl-2 mRNA open reading frame.

Increase of sural nerve T cells in progressive axonal polyneuropathy and monoclonal gammopathy.

The authors investigated whether T cells have a role in the pathogenesis of axonal polyneuropathy and monoclonal gammopathy by comparing the presence of T cells in sural nerves of 23 patients with axonal polyneuropathy and monoclonal gammopathy (12 IgM, 11 IgG), of 15 patients with chronic idiopathic axonal polyneuropathy, and of 10 autopsy cases. Seven patients with an increased T-cell density had a progressive disease course, and four of these patients were treated with prednisone with a good response, suggesting that vasculitis plays a role in the pathogenesis.

Sural nerve T cells in demyelinating polyneuropathy associated with monoclonal gammopathy.

The clinical presentation of polyneuropathy associated with monoclonal gammopathy is heterogeneous. As T cells in sural nerve biopsy specimens may represent a marker of inflammation, we analyzed whether the presence of sural nerve T cells in patients with demyelinating polyneuropathy associated with monoclonal gammopathy may help to define a specific clinical entity. Using immunohistochemical analysis we investigated the number and distribution of sural nerve T cells in 18 patients with polyneuropathy associated with IgM monoclonal gammopathy (including 14 with antibodies to the myelin-associated glycoprotein) and 7 with IgG monoclonal gammopathy, and compared them with sural nerves of 23 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 15 patients with chronic idiopathic axonal polyneuropathy (CIAP), and 10 normal controls.

[Totally paralyzed or brain dead?].

In two patients, men aged 23 and 42 years, a condition that mimicked brain death was observed as a consequence of rapidly progressive complete peripheral paralyses, which included the intrinsic and extrinsic eye muscles. However, the EEG revealed a waking pattern. Maximal supportive therapy was provided, which included haemodialysis for the first patient and artificial ventilation for both patients.

Painful ophthalmoplegia from metastatic nonproducing parathyroid carcinoma: case study and review of the literature.

Parathyroid carcinoma is an uncommon malignancy. Of the fewer than 400 cases reported, most have been cases of producing parathyroid carcinoma with accompanying hypercalcemia. Only 13 patients with nonproducing parathyroid carcinoma have been described.

Antiganglioside antibodies in polyneuropathy associated with monoclonal gammopathy.

Antibody reactivity to GA1, GM1, GM2, GD1a, GD1b, and GQ1b gangliosides was measured in 87 patients with polyneuropathy associated with monoclonal gammopathy (60 IgM, 25 IgG, 2 IgA) and 42 control patients with monoclonal gammopathy without polyneuropathy (21 IgM, 21 IgG). Of these 87 patients, 30% had anti-myelin-associated glycoprotein antibodies and 15% had antiganglioside antibodies. Antiganglioside antibodies were significantly associated with demyelinating neuropathy and with IgM monoclonal gammopathy.

Malignant transformation of monoclonal gammopathy of undetermined significance: cumulative incidence and prognostic factors.

The cumulative incidence of malignant transformation was studied in 88 patients with monoclonal gammopathy of undetermined significance (MGUS) that had a complete prospective follow-up. At a median follow-up of 6.75 years, 10 patients developed multiple myeloma (MM) (11.