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1.
Epilepsy Behav Rep ; 21: 100574, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36545476

RESUMO

We retrospectively studied the efficacy and tolerability of lacosamide (LCM) in children with drug-resistant epilepsy in a tertiary care centre in the Netherlands, from 2013 till 2019, with a follow-up of two years. 79 children, aged < 18 years, were included. Retention rate, effectiveness, reason for termination, and side-effects were analysed. Furthermore, prognostic variables for discontinuation as well as the incidence of side-effects were determined. The LCM retention rate and effectiveness of response were analysed at three, twelve and twenty-four months. The retention rate of LCM was respectively 89.9 %, 68.4 % and 54.4 %. LCM gave an effective response in 60.5 %, 67.9 % and 71.4 % of the participants who were still using LCM at the three follow-up periods. Lack of efficacy was most frequently reported as a reason for discontinuation (58.3 %). Side-effects occurred in 50.6 % of the patients, somnolence (18.2 %) being the most common, followed by behavioural changes (15.6 %), headache (9.1 %) and dizziness (9.1 %). Use of ≥ 1 sodium channel blocker (SCB) was associated with an increased risk (OR = 4.038) of side-effects. An increasing number of anti-seizure medications (ASM) was associated with a reduced risk (OR = 0.524) of stopping LCM. To conclude, LCM is an effective ASM with acceptable side-effects in children with drug-resistant epilepsy.

2.
Seizure ; 103: 32-38, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36270136

RESUMO

PURPOSE: The aim of this longitudinal study was to assess trabecular bone scores (TBS) in institutionalized adults with refractory epilepsy and intellectual disability and to study the association of TBS and incident fractures during seven years of follow-up. METHODS: In 2009 and 2016, all institutionalized adult patients of a long-stay care facility in the Netherlands (n=261) were invited to undergo a dual-energy X-ray absorptiometry (DXA) including vertebral fracture assessment (VFA) and assessment of TBS. Vertebrae T4-L4 were analyzed using quantitative morphometry. New and worsening vertebral fractures (VFs) were considered as incident VFs. Data regarding clinical fractures were extracted from the medical files. Patients were treated with anti-osteoporosis medication according to the Dutch guideline. RESULTS: Baseline and follow-up DXA, VFA and TBS could be obtained in 136 patients (83 male) aged between 18 and 79 years old (44.7±15.5). At baseline, 36 patients (26.5%) were diagnosed with osteoporosis, 68 (50.0%) with osteopenia and 32 patients (23.5%) had a normal bone mineral density (BMD). As for TBS, 26 patients (19.1%) had a partially degraded microarchitecture and 26 patients (19.1%) a degraded microarchitecture. During seven years of follow-up, 80 patients (59%) sustained at least one fracture, of which 28 patients (35%) had one or more major osteoporotic fractures. Thirty-four patients (25.0%) had at least one new or worsening morphometric VF. Compared to baseline, TBS significantly decreased over seven years of follow-up in non-treated patients (-0.039±0.064, p<.001). In patients who were treated with bisphosphonates for more than one year during follow-up, TBS did not change significantly (p=.093). In multivariate analyses, no significant associations were found between TBS at baseline and incident fractures during follow-up. CONCLUSION: In this study, we found a high incidence of fractures and TBS decreased significantly over seven years of follow-up in non-treated institutionalized adult patients with refractory epilepsy and intellectual disability, but TBS was not associated with incident fractures.


Assuntos
Epilepsia Resistente a Medicamentos , Deficiência Intelectual , Fraturas da Coluna Vertebral , Adulto , Humanos , Masculino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Osso Esponjoso/diagnóstico por imagem , Seguimentos , Epilepsia Resistente a Medicamentos/complicações , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/complicações , Estudos Longitudinais , Vértebras Lombares , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/epidemiologia , Densidade Óssea
3.
J Intellect Disabil Res ; 65(11): 962-970, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34472148

RESUMO

BACKGROUND: Long-term use of antiseizure drugs is associated with a low bone mineral density (BMD) and an increased fracture risk. The literature regarding institutionalised children on chronic antiseizure drugs is limited. Therefore, the aim of this cross-sectional study is to evaluate the prevalence of low BMD and the history of fractures in institutionalised children with epilepsy and intellectual disability (ID). METHODS: A dual-energy X-ray absorptiometry of lumbar spine (L1-L4) and hip was performed in 24 children, residing in a long-stay care facility in the Netherlands. Additionally, serum concentrations of albumin, calcium and 25-hydroxyvitamin D were determined. Data on fractures were retrospectively extracted from the medical files. RESULTS: Ages of the children (14 male and 10 female) ranged from 5 to 17 years with a mean age of 13.0 (±3.2). The criteria of the International Society for Clinical Densitometry (ISCD) were used for classification of bone mineral disorders. Eight (33.3%) children had a normal BMD (Z-score > - 2.0). Of the 16 children with a low BMD (Z-score ≤ - 2.0), three were diagnosed as osteoporotic, based on their fracture history. Ten children (41.7%) were reported to have at least one fracture in their medical history. Serum concentrations of albumin-corrected calcium (2.28-2.50 mmol/L) and (supplemented) vitamin D (16-137 nmol/L) were within the normal range. CONCLUSIONS: This study demonstrated that 67% of institutionalised children with epilepsy and ID had low BMD and 42% had a history of at least one fracture, despite supplementation of calcium and vitamin D in accordance with the Dutch guidelines.


Assuntos
Epilepsia , Deficiência Intelectual , Osteoporose , Adolescente , Densidade Óssea , Criança , Criança Institucionalizada , Pré-Escolar , Estudos Transversais , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Estudos Retrospectivos
4.
Seizure ; 92: 56-61, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34438165

RESUMO

PURPOSE: To determine the incidence of clinical fractures over seven years of follow-up, in adults with epilepsy and intellectual disability, residing in a long-stay care facility. METHODS: In 2009, all institutionalized adult patients (n = 261) were invited to undergo a Dual-energy X-ray Absorptiometry (DXA) measurement and a Vertebral Fracture Assessment (VFA). Participants were followed over seven years or until date of discharge (in case of moving from the care facility) or date of death. The patients' medical files were screened for radiology reports and staff notes, to identify clinical fractures. Fracture incidence rates (IR) were determined and compared for subgroups, by calculating incidence rate ratios. Hazard ratios were calculated to identify factors associated with fracture risk, using Cox Proportional Hazards analyses. RESULTS: A total of 205 patients (124 male, 60.5%) aged between 18 and 88 years (median 48, IQR 34-60) were enrolled. At baseline, 92 patients (44.9%) were diagnosed with osteopenia and 65 (31.7%) with osteoporosis. Between 2009 and 2016, 30 patients (14.6%) deceased and 3 patients (1.5%) left the care facility. During follow-up, 156 clinical fractures were reported in 82 patients (40.0%). Thirty-eight patients (18.5%) had at least one major osteoporotic fracture. Overall, the IR was 11.6 fractures per 100 person-years. Fracture risk was significantly lower in patients who were wheelchair dependent than in patients who were able to walk (p<.001). CONCLUSION: This study demonstrated that 40% of institutionalized adults with epilepsy and intellectual disability had at least one clinical fracture during seven years of follow-up, despite adequate anti-osteoporosis treatment.


Assuntos
Epilepsia , Deficiência Intelectual , Fraturas por Osteoporose , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Epilepsia/epidemiologia , Seguimentos , Humanos , Incidência , Deficiência Intelectual/complicações , Deficiência Intelectual/epidemiologia , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Adulto Jovem
5.
Seizure ; 71: 35-41, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31203025

RESUMO

PURPOSE: Long-term exposure to anti-epileptic drugs has been shown to decrease bone mineral density (BMD). The aim of this 7-year follow-up study was to explore changes in bone status, using quantitative ultrasound (QUS) and Dual-energy X-ray Absorptiometry (DXA) in adults with refractory epilepsy and intellectual disability (ID) residing at a long-term care facility. Both measurements can be challenging to conduct in this population. METHODS: In 2009 and 2016, a total of 126 patients (18-79 years) underwent QUS of the heel and DXA of lumbar spine (LS) and hip (femoral neck (FN) and total hip (TH)). Subgroup analysis was performed for patients with (group A, n = 53) and without (group B, n = 73) bisphosphonate use during follow-up. RESULTS: Overall, weak to moderate correlations between changes in DXA and QUS parameters were found. For group A, correlations varied from r = .31 to .59, whereas correlations did not exceed r = .40 in group B. Patients in group A showed a larger increase or a smaller decrease in BMD for all DXA regions during follow-up (p < .001 for ΔLS and ΔFN BMD, p = .001 for ΔTH BMD). For change in QUS parameters, no significant difference between groups was found. CONCLUSION: In this study we demonstrated the limited use of QUS in the monitoring of bone status in our study population. Although correlations between changes in QUS parameters and axial DXA are positive and mostly significant, QUS only explains little of the variability in DXA values and is inadequate for measuring treatment response in this population.


Assuntos
Absorciometria de Fóton/normas , Anticonvulsivantes/efeitos adversos , Densidade Óssea , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Deficiência Intelectual , Ultrassonografia/normas , Adolescente , Adulto , Idoso , Comorbidade , Difosfonatos/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/epidemiologia , Feminino , Seguimentos , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Epilepsy Behav ; 37: 133-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25022821

RESUMO

BACKGROUND: The mechanism of action of vagus nerve stimulation (VNS) in intractable epilepsy is not entirely clarified. It is believed that VNS causes alterations in cytokines, which can lead to rebalancing the release of neurotoxic and neuroprotective tryptophan metabolites. We aimed to evaluate VNS effects on tryptophan metabolites and on epileptic seizures and investigated whether the antiepileptic effectiveness correlated with changes in tryptophan metabolism. METHODS: Forty-one children with intractable epilepsy were included in a randomized, active-controlled, double-blind study. After a baseline period of 12 weeks, all children underwent implantation of a vagus nerve stimulator and entered a blinded active-controlled phase of 20 weeks. Half of the children received high-output (therapeutic) stimulation (n=21), while the other half received low-output (active control) stimulation (n=20). Subsequently, all children received high-output stimulation for another 19 weeks (add-on phase). Tryptophan metabolites were assessed in plasma and cerebrospinal fluid (CSF) by use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared between high- and low-output groups and between the end of both study phases and baseline. Seizure frequency was recorded using seizure diaries. Mood was assessed using Profile of Mood States (POMS) questionnaires. RESULTS: Regarding tryptophan metabolites, anthranilic acid (AA) levels were significantly higher at the end of the add-on phase compared with baseline (p=0.002) and correlated significantly with improvement of mood (τ=-0.39, p=0.037) and seizure frequency reduction (τ=-0.33, p<0.01). No significant changes were found between high- and low-output groups regarding seizure frequency. CONCLUSION: Vagus nerve stimulation induces a consistent increase in AA, a neuroprotective and anticonvulsant tryptophan metabolite. Moreover, increased AA levels are associated with improvement in mood and reduction of seizure frequency.


Assuntos
Epilepsia/metabolismo , Epilepsia/terapia , Triptofano/metabolismo , Estimulação do Nervo Vago/métodos , Adolescente , Afeto , Biotransformação , Criança , Pré-Escolar , Método Duplo-Cego , Resistência a Medicamentos , Eletrodos Implantados , Feminino , Humanos , Cinurenina/metabolismo , Masculino , Redes e Vias Metabólicas , Convulsões/epidemiologia , Convulsões/prevenção & controle , Resultado do Tratamento , Triptofano/sangue , Triptofano/líquido cefalorraquidiano , ortoaminobenzoatos/líquido cefalorraquidiano , ortoaminobenzoatos/metabolismo
7.
Acta Neurol Scand ; 128(4): 273-80, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23461582

RESUMO

PURPOSE: Long-term antiepileptic drug use is associated with low bone mineral density (BMD), fractures and abnormalities in bone metabolism. We aimed at determining the prevalence of bone mineral disorders in patients with refractory epilepsy treated with antiepileptic drugs. METHODS: A cross-sectional survey was conducted in adult patients (n = 205) from a residential unit of a tertiary epilepsy centre. Screening for bone mineral disorders was performed with dual-energy X-ray absorptiometry (DXA) scan of spine and hip (including bone mineral density and vertebral fracture assessment) and laboratory measurements. Patient information regarding demography, epilepsy characteristics and medication use was recorded. Based on DXA T-scores, prevalence of bone mineral disorders (osteopenia and osteoporosis) was calculated. Correlations between DXA T-scores and epilepsy parameters were explored. RESULTS: Of the 205 patients, there were 10 dropouts. 80% (n = 156/195) of the patients had low BMD: 48.2% had osteopenia and 31.8% had osteoporosis. Of those having low BMD, 51.9% (n = 81/195) was between 18 and 50 years. The T-score of the femoral neck correlated significantly with total duration of epilepsy, cumulative drug load and history of fractures. Linear regression analysis showed that of the epilepsy-related parameters, only cumulative drug load significantly predicted low femoral neck T-score (P = 0.001). CONCLUSION: In this high-risk population, we obtained a very high prevalence of 80% of low BMD. Both men and women were affected as well as patients <50 years of age. This study illustrates the magnitude of the problem of bone mineral disorders in chronic epilepsy.


Assuntos
Anticonvulsivantes/efeitos adversos , Doenças Ósseas Metabólicas/induzido quimicamente , Doenças Ósseas Metabólicas/epidemiologia , Pacientes Internados , Osteoporose/induzido quimicamente , Osteoporose/epidemiologia , Absorciometria de Fóton , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Doença Crônica/tratamento farmacológico , Estudos Transversais , Epilepsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Regressão , Adulto Jovem
8.
Biochim Biophys Acta ; 1520(1): 1-6, 2001 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-11470154

RESUMO

Using search profiles based on the conserved alpha-crystallin domain that is characteristic for small heat shock proteins (sHsps), we traced two new human sHsps. One of these, being the eighth known human sHsp and thus named HspB8, was recently described as a serine-threonine protein kinase (H11), but not identified as an sHsp (C.C. Smith, Y.X. Yu, M. Kulka, L. Aurelian, J. Biol. Chem. 275 (2000)). Northern blotting showed that HspB8/H11 is predominantly transcribed in skeletal muscle and heart, like most other sHsps. The other, named HspB9, is specifically expressed in testis, notably in the spermatogenic cells from late pachytene spermatocyte stage till elongate spermatid stage. While mammalian sHsps are generally highly conserved, mouse HspB9 shows 38% sequence difference with human HspB9, which may confirm its sex-related role.


Assuntos
Proteínas de Choque Térmico/química , Proteínas Serina-Treonina Quinases/química , Sequência de Aminoácidos , Animais , DNA Complementar/isolamento & purificação , Humanos , Hibridização In Situ , Masculino , Camundongos , Chaperonas Moleculares , Dados de Sequência Molecular , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/análise , Alinhamento de Sequência , Testículo/metabolismo
9.
Biochem Biophys Res Commun ; 262(1): 152-6, 1999 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-10448084

RESUMO

Amyloid beta (Abeta) is a 40- to 42-residue peptide that is implicated in the pathogenesis of Alzheimer's Disease (AD). As a result of conformational changes, Abeta assembles into neurotoxic fibrils deposited as 'plaques' in the diseased brain. In AD brains, the small heat shock proteins (sHsps) alphaB-crystallin and Hsp27 occur at increased levels and colocalize with these plaques. In vitro, sHsps act as molecular chaperones that recognize unfolding peptides and prevent their aggregation. The presence of sHsps in AD brains may thus reflect an attempt to prevent amyloid fibril formation and toxicity. Here we report that alphaB-crystallin does indeed prevent in vitro fibril formation of Abeta(1-40). However, rather than protecting cultured neurons against Abeta(1-40) toxicity, alphaB-crystallin actually increases the toxic effect. This indicates that the interaction of alphaB-crystallin with conformationally altering Abeta(1-40) may keep the latter in a nonfibrillar, yet highly toxic form.


Assuntos
Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/toxicidade , Cristalinas/farmacologia , Chaperonas Moleculares/farmacologia , Neurônios/patologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/toxicidade , Placa Amiloide/efeitos dos fármacos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Benzotiazóis , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral , Relação Dose-Resposta a Droga , Hipocampo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/ultraestrutura , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Placa Amiloide/ultraestrutura , Ligação Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína/efeitos dos fármacos , Ratos , Tiazóis
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