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1.
J Neurol Neurosurg Psychiatry ; 95(5): 392-400, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37963723

RESUMO

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. Adults with a diagnosis of relapsing-remitting MS who received ≥6 natalizumab infusions were included in three groups: personalised EID with a target drug trough concentration of 10 µg/mL (EID10), an exploratory group of personalised EID with a target of 5 µg/mL (EID5) and standard interval dosing (SID) of 4 weeks. The primary outcome is radiological disease activity (new/newly enlarged T2 lesions) comparing the EID10 group to a historical cohort of SID (HSID). RESULTS: Results of the first phase of the NEXT-MS trial are reported here (n=376) as the study will continue with an amended protocol. In the EID10 group (n=251), incidence rate of radiological activity was 10.0 per 1000 person-years, which was non-inferior to the HSID cohort (24.7 per 1000 person-years (n=87), incidence rate difference 14.7, 90% CI -4.5 to 34.0). Incidence rate of radiological activity was 10.0 per 1000 person-years in the EID5 group (n=65), and 47.0 per 1000 person-years in the SID group (n=60). Serum neurofilament light levels did not increase over time within the EID groups. There were no cases of progressive multifocal leukoencephalopathy. CONCLUSIONS: MS disease activity is adequately controlled with personalised natalizumab EID. Interval extension to a drug trough concentration of 5 µg/mL is likely a safe target to extend natalizumab treatment intervals >6 weeks. TRIAL REGISTRATION NUMBER: NCT04225312.


Assuntos
Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Humanos , Monitoramento de Medicamentos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Leucoencefalopatia Multifocal Progressiva/etiologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/complicações , Natalizumab/uso terapêutico , Estudos Prospectivos
2.
Ann Hematol ; 96(4): 653-663, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28116479

RESUMO

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. Fifty-three percent of patients reported at least one and on average three neuropathy symptoms that bothered them the most during the past week, with tingling toes/feet as most reported. In multivariate analysis, thalidomide, especially higher cumulative dose, was associated with neuropathy (ß = 0.26, CI 95% 0.27-15.34, p = 0.04) and CIPN was not associated with age, sex, time since last course of therapy, number of prior therapies, osteoarthritis, or diabetes. Dose modifications were often applied (65%). Although not statistically significant, a trend towards higher sensory (22 vs. 15 vs. 12, p = 0.22) and motor neuropathy scores (21 vs. 15 vs. 11, p = 0.36) was observed among patients receiving dose modification because of CIPN (31%) compared to those receiving a dose modification for another reason or no dose modification, without altering treatment response. CIPN is a common dose limiting side effect in patients with MM. Severity of CIPN was mainly affected by treatment with thalidomide. In spite of dose modifications, patients still reported somewhat higher neuropathy scores without altered response rates. Early dose modification based on a more reliable tool for CIPN measurements may prove value.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Vigilância da População , Sistema de Registros , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Países Baixos/epidemiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/epidemiologia , Vigilância da População/métodos , Estudos Prospectivos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
3.
Ned Tijdschr Geneeskd ; 158: A8030, 2014.
Artigo em Holandês | MEDLINE | ID: mdl-25387982

RESUMO

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. The diagnosis was confirmed by electroencephalography (EEG). The medical history mentioned previous episodes of changes in behaviour in all patients. The 14-year-old boy was diagnosed with attention deficit hyperactivity disorder (ADHD). It is questionable whether this diagnosis was justified, or whether his behavioural problems were caused by non-convulsive epileptic seizures. Non-convulsive status epilepticus is characterised by diminished cognitive functioning in an otherwise reactive patient. Testing of memory and other cognitive functions is essential for diagnosis. All children with behavioural problems should undergo a thorough neurological assessment by a paediatrician or neurologist in order to recognise non-convulsive epilepsy.


Assuntos
Comportamento do Adolescente , Estado Epiléptico/diagnóstico , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Cognição/fisiologia , Diagnóstico Diferencial , Eletroencefalografia , Humanos , Masculino , Memória/fisiologia
4.
J Neuroimmunol ; 268(1-2): 89-94, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24529728

RESUMO

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. IgM antibodies against gangliosides activated complement in vitro. Light chain usage was restricted to kappa or lambda in most, but not all patients. In conclusion, anti-ganglioside antibodies in IgM-PNP are common, display pathogenic properties and do not always arise from a monoclonal B cell proliferation.


Assuntos
Autoanticorpos/sangue , Autoanticorpos/imunologia , Gangliosídeos/imunologia , Imunoglobulina M/imunologia , Paraproteinemias/imunologia , Polineuropatias/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Especificidade de Anticorpos/imunologia , Autoantígenos/imunologia , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Paraproteinemias/sangue , Paraproteinemias/epidemiologia , Polineuropatias/sangue , Prevalência
5.
Brain ; 135(Pt 5): 1639-49, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22189568

RESUMO

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. A total of 1065 patients were included from nine cohorts with the following diseases: Guillain-Barré syndrome (n = 480); myotonic dystrophy type-1 (n = 169); chronic inflammatory demyelinating polyradiculoneuropathy (n = 139); limb-girdle muscular dystrophy (n = 105); multifocal motor neuropathy (n = 102); Pompe's disease (n = 62) and monoclonal gammopathy of undetermined related polyneuropathy (n = 8). Medical Research Council data of 72 muscles were collected. Rasch analyses were performed on Medical Research Council data for each cohort separately and after pooling data at the muscle level to increase category frequencies, and on the Medical Research Council sum score in patients with Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Disordered thresholds were demonstrated in 74-79% of the muscles examined, indicating physicians' inability to discriminate between most Medical Research Council categories. Factors such as physicians' experience or illness type did not influence these findings. Thresholds were restored after rescoring the Medical Research Council grades from six to four options (0, paralysis; 1, severe weakness; 2, slight weakness; 3, normal strength). The Medical Research Council sum score acceptably fulfilled Rasch model expectations after rescoring the response options and creating subsets to resolve local dependency and item bias on diagnosis. In conclusion, a modified, Rasch-built four response category Medical Research Council grading system is proposed, resolving clinicians' inability to differentiate among its original response categories and improving clinical applicability. A modified Medical Research Council sum score at the interval level is presented and is recommended for future studies in Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.


Assuntos
Pesquisa Biomédica , Conselhos de Planejamento em Saúde/normas , Força Muscular/fisiologia , Doenças Musculares/diagnóstico , Doenças Musculares/fisiopatologia , Adolescente , Adulto , Viés , Criança , Pré-Escolar , Feminino , Conselhos de Planejamento em Saúde/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Doenças Musculares/classificação , Doenças Musculares/epidemiologia , Adulto Jovem
6.
J Neurol Sci ; 260(1-2): 124-31, 2007 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-17543994

RESUMO

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. Cytogenetic aberrations may be found in one third of the patients with neuropathy associated with IgM monoclonal gammopathy and are mainly associated with indolent Waldenstrom's Macroglobulinemia.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 14/genética , Predisposição Genética para Doença/genética , Imunoglobulina M/genética , Paraproteinemias/genética , Polineuropatias/genética , Idoso , Linfócitos B/imunologia , Análise Mutacional de DNA , Feminino , Testes Genéticos , Genótipo , Humanos , Imunoglobulina M/imunologia , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Paraproteinemias/imunologia , Paraproteinemias/fisiopatologia , Nervos Periféricos/imunologia , Nervos Periféricos/fisiopatologia , Polineuropatias/imunologia , Polineuropatias/fisiopatologia , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/imunologia , Macroglobulinemia de Waldenstrom/fisiopatologia
7.
J Neuroimmunol ; 175(1-2): 152-9, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16600385

RESUMO

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. V genes associated with bacterial responses appear over-represented and V(H)3-23 was preferentially used, without association with specific D, J(H) or V(L)J(L). V genes revealed somatic mutation and intraclonal variation was found in 9 of 20 patients. Polyneuropathy associated with monoclonal gammopathy may be caused by an immune response to bacterial antigens, which recruit somatically mutated autoreactive B cells.


Assuntos
Genes de Imunoglobulinas , Imunoglobulina M/genética , Paraproteinemias/genética , Polineuropatias/genética , Idoso , Subpopulações de Linfócitos B/química , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Células Clonais , Feminino , Humanos , Imunoglobulina M/química , Cadeias kappa de Imunoglobulina/genética , Cadeias lambda de Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , Paraproteinemias/complicações , Paraproteinemias/metabolismo , Polineuropatias/complicações , Polineuropatias/metabolismo , Análise de Sequência de DNA
8.
Neuro Oncol ; 4(1): 44-8, 2002 01.
Artigo em Inglês | MEDLINE | ID: mdl-11772432

RESUMO

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. Nine of these 13 patients had metastatic disease. We report a patient with i.c. metastasis. Distal metastases of producing parathyroid carcinoma are treated surgically to prolong survival and prevent complications of hyperparathyroidism and hypercalcemia. One half of the patients with producing parathyroid carcinoma die within 5 years, mostly because of the complications of hypercalcemia. Nonproducing parathyroid carcinoma compares unfavorably with producing parathyroid carcinoma in terms of tumor progression and prognosis. Few data on choice of therapy in nonproducing parathyroid carcinoma are available. We treated our patient with a combination of radiotherapy and chemotherapy. Treatment was followed by an unexpectedly prolonged survival of 31 months after diagnosis of metastatic disease.


Assuntos
Neoplasias Encefálicas/complicações , Carcinoma/complicações , Carcinoma/secundário , Oftalmoplegia/etiologia , Oftalmoplegia/fisiopatologia , Neoplasias das Paratireoides/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Carcinoma/radioterapia , Terapia Combinada , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Dor/fisiopatologia , Resultado do Tratamento
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