Biomedical subjects

M Eurelings

Publications and source records attributed to M Eurelings.

13 recordsLinked to original sources

PubMed2006

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. Hematologic response in bone marrow occurred in three of five of these patients, whereas two of five already had small polyclonal B cell populations. There were no serious side effects.

Aged↗

PubMed2005

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. The incidence rate of malignant transformation in 176 patients without a malignancy at diagnosis was 2.7/100 patient years. Weight loss, progression of the polyneuropathy, unexplained fever or night sweats, and M-protein level were independent predictors. CONCLUSIONS: Since hematologic malignancies occur frequently in polyneuropathy associated with monoclonal gammopathy, the authors suggest that all patients should be screened at diagnosis and subsequently during follow-up if malignant transformation is suspected.

Aged↗

PubMed2004

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. In this study, G3139 was delivered as a continuous intravenous infusion for 7 days at a fixed dose of 7 mg/kg/day in combination with VAD (vincristine, adriamycin, and dexamethasone) chemotherapy. In total, 10 heavily pretreated patients with refractory myeloma participated in this trial, including eight patients with VAD refractory disease. The combination of G3139 and VAD was feasible and well tolerated. Seven patients (70%) responded including four patients (40%) with a partial response and three patients (30%) with a minor response. Median progression-free survival was 6 months (range, 2-7+ months) and median overall survival has not been reached. G3139 downregulated Bcl-2 protein levels in peripheral blood circulating myeloma cells, B cells, T cells, and monocytes. These results indicate that G3139 may overcome classical resistance and restore sensitivity of myeloma tumor cells to VAD chemotherapy.

Adult↗

PubMed2003

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.

Axons↗

PubMed2001

[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. A slow recovery was seen after four weeks. The first patient was paralyzed following the ingestion of a large quantity of ethylene glycol and the second by botulism due to the consumption of injudiciously canned food. In patients with catastrophic brain injury, the diagnosis of brain death can be confirmed by a clinical neurological examination. In considering the diagnosis 'brain death', the most important criterion is that the cause of the brain damage is established. If the cause is insufficiently, the presence of brain death should be seriously doubted, unless an isoelectric EEG is observed.

Adult↗

PubMed2001

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. Anti-GD1b and anti-GQ1b antibodies were significantly associated with predominantly sensory ataxic neuropathy.

Adult↗

PubMed2001

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. Six patients with polyneuropathy associated with monoclonal gammopathy had increased T cell densities compared with CIAP patients and normal controls. No differences were found in distribution or phenotype of the T cells. T cell densities in patients with IgM monoclonal gammopathy were significantly lower than in patients with IgG monoclonal gammopathy or with CIDP. Increased sural nerve T cells were significantly associated with a subset of patients who had a more progressive disease course and more pronounced weakness. Increased sural nerve T cells were found significantly more often in patients with a monoclonal gammopathy of the IgG isotype, which was frequently associated with hematological malignancy.

Adult↗

PubMed2001

Neuropathy and IgM M-proteins: prognostic value of antibodies to MAG, SGPG, and sulfatide.

BACKGROUND: In polyneuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy, antibodies to myelin-associated glycoprotein (MAG), sulfoglucuronyl paragloboside (SGPG), and sulfatide have been associated with specific clinical and electrophysiologic features. However, it is not known whether the results of antibody tests provide additional information for the individual patient (and the neurologist) in terms of future neurologic deficit or outcome. OBJECTIVE: To study the independent contribution of potential prognostic factors to the prediction of outcome of neuropathy associated with IgM monoclonal gammopathy. METHODS: In accordance with the chronology in which prognostic factors are available in clinical practice, the association between prognostic factors and outcome was evaluated by univariate and multivariate logistic regression analysis in 65 patients with polyneuropathy and IgM monoclonal gammopathy. RESULTS: In univariate analysis, the initial symptoms, the IgM light chain type, electrophysiologic and pathologic studies, the presence of sural nerve IgM deposition, and anti-MAG or anti-SGPG antibodies were significantly associated with outcome. However, multivariate analysis showed that only initial symptoms and electrophysiologic studies are independent prognostic factors: initial sensory symptoms of the feet are prognostic for a slowly progressive disease course and less disability at 4 years, and evidence for demyelination on electrophysiologic examination is prognostic for development of weakness and symptoms of the upper extremities at 4 years. Addition of anti-MAG or anti-SGPG antibody tests did not yield any additional prediction of outcome. CONCLUSION: These results indicate that in clinical practice, antibody tests in polyneuropathy associated with IgM monoclonal gammopathy do not have a prognostic value in terms of future neurologic deficit or outcome.

Globosides↗

PubMed2001

Risk factors for hematological malignancy in polyneuropathy associated with monoclonal gammopathy.

Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) is a well-known disease entity. Of the patients with monoclonal gammopathy without neuropathy, 25% develop a hematological malignancy during long-term follow-up. Whether the frequency of hematological malignancy is similar in patients with polyneuropathy associated with monoclonal gammopathy and whether hematological screening is necessary in these patients is unknown. To determine the frequency of and risk factors for a hematological malignancy, we investigated 104 patients with polyneuropathy and monoclonal gammopathy. Potential diagnostic variables were obtained from medical history, physical and neurological examination, and laboratory analysis. The associations between potential diagnostic variables and outcome, hematological malignancy, were evaluated by univariable and multivariable logistic-regression analysis. Among our patients, 23 had a hematological malignancy (8 multiple myeloma, 10 low-grade lymphoma, 3 plasmacytoma, 1 Castleman's disease and 1 POEMS syndrome [polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes]). Weight loss, progression of the neuropathy, and an M-protein level > 1 g/L were independent risk factors for malignancy. Extensive screening is indicated in patients with these features.

Adult↗

PubMed2001

MRI of the brachial plexus in polyneuropathy associated with monoclonal gammopathy.

On magnetic resonance (MR) imaging of the brachial plexus increased signal intensity and swelling of the brachial plexus has been found in chronic inflammatory demyelinating polyneuropathy (CIDP). Whether these proximal abnormalities are also present in the distal polyneuropathy associated with monoclonal gammopathy is unknown. Therefore, we performed MR imaging of the brachial plexus in 21 patients with polyneuropathy associated with IgM monoclonal gammopathy (11 IgM with anti-MAG antibodies, 10 IgM without anti-MAG antibodies). For comparison we studied 9 patients with polyneuropathy associated with IgG monoclonal gammopathy and 8 patients with CIDP. Among the 30 patients with monoclonal gammopathy, 24 patients had demyelinating polyneuropathy. Among these 24 patients, there was increased signal intensity of the brachial plexus on the T2-weighted images regardless of whether clinical deficits were generalized or purely distal in location. No association was found with the isotype of the monoclonal gammopathy. Of the 8 patients with CIDP, 5 had brachial plexus abnormalities. None of the 6 patients with axonal polyneuropathy associated with monoclonal gammopathy had such abnormalities. Thus, MR imaging of the brachial plexus shows that the distal demyelinating polyneuropathy associated with monoclonal gammopathy is more generalized than presumed.

Adult↗

PubMed2001

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) (11.4%) and 2 developed immunocytoma (2.3%). The cumulative incidence of malignant transformation was 9.1, 21.3, 38 and 48.3% at 5, 10, 15 and 20 years, respectively. In univariate analysis on 102 MGUS patients, M-component level, bone marrow plasma cell percentage and kappa light chain correlated significantly with the development of a malignancy (p=0.0289, 0.0265 and 0.0013, respectively). In multivariate analysis, light chain type of M-component and plasma cell percentage had independent prognostic significance. A high-risk (M-component level > 10 g/l and/or plasma cell percentage > 2%) and a low-risk group ( M-component level < 10 g/l and/or plasma cell percentage < 2%) of MGUS patients was identified, which differed significantly in the cumulative incidence of developing a malignancy (p<0.001 for M-component level and p=0.007 for plasma cell percentage). These results imply that high-risk patients should receive a more frequent follow-up, in comparison to low-risk patients.

Adult↗

PubMed2000

Diagnostic criteria for demyelinating polyneuropathy associated with monoclonal gammopathy.

In order to define diagnostic criteria for the demyelinating polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS), we compared 30 patients with idiopathic chronic inflammatory demyelinating polyneuropathy (CIDP) without a monoclonal gammopathy, with 29 patients with polyneuropathy associated with MGUS. All 59 patients fulfilled research criteria for CIDP. In the patients with MGUS, sensory symptoms and signs predominated, there was usually no cranial nerve involvement, and the neuropathy was symmetrical with a slowly progressive course. On electrophysiological examination, an abnormal median nerve sensory action potential in combination with a normal sural nerve action potential (AMNS) was not found. In idiopathic CIDP patients, a preceding infection was frequent, motor features predominated, there was often cranial nerve involvement, the neuropathy could be asymmetrical, and AMNS was frequently found. Diagnostic criteria for demyelinating polyneuropathy associated with MGUS are presented.

Action Potentials↗

PubMed2000

Quality of life in patients with axonal polyneuropathy.

"Quality of life" (QOL) measurement reflects the impact of a disease on the daily life of a patient, and this can be used as an outcome measure in clinical trials. QOL measurements are rarely used in patients with neuromuscular disease. The aim of this study was to determine whether QOL is reduced in chronic polyneuropathy, whether there is a relationship between QOL and objective measures of disease severity, and whether measuring QOL is a useful addition to the assessment of severity of polyneuropathy. We measured QOL in 90 patients with chronic axonal polyneuropathy (33 with hereditary motor and sensory neuropathy type II and 57 with chronic idiopathic axonal polyneuropathy) using the RAND 36-item Health Survey questionnaire (RAND-36). We compared the results with the QOL of a reference population, with summed motor and sensory scores, and with the Rankin scale for handicap. Patients had worse scores than the reference population on seven of eight areas of the RAND-36. Patients with both low motor and low sensory scores rated lower in physical and emotional areas than less impaired patients. A low Rankin score was related only to physical domains. We conclude that in patients with chronic axonal polyneuropathy the severity of disease can be assessed with a general QOL instrument, and that this provides additional information, particularly on areas related to emotional and social functioning.

Aged↗