RESUMO
Ocrelizumab is a novel humanized anti-CD20 antibody used for treatment of relapsing remitting and primary progressive multiple sclerosis with evidence of inflammatory activity. Guidelines suggest assessing vaccination status and eventually vaccinate patients with multiple sclerosis before new disease modifying therapy initiation. However, there are not any specific recommendations about vaccinal immunity reassessment after ocrelizumab injection. We describe the case of a patient who loss varicella zoster vaccinal immunity after the first ocrelizumab infusion. It is advisable to reassess vaccinal immunity to isolate non-immune patients and to adopt suitable preventive measures, including close contacts vaccination and avoidance of contacts with active infection.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Herpesvirus Humano 3/fisiologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Infecção pelo Vírus da Varicela-Zoster/imunologia , Antígenos CD20/imunologia , Linfócitos B/imunologia , Humanos , Imunidade Humoral , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Ativação Viral , Latência ViralRESUMO
OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses' professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it.
Assuntos
Esclerose Múltipla , Qualidade de Vida , Estudos Transversais , Empatia , Feminino , Humanos , Itália/epidemiologia , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients. The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting. METHODS: We collected data of all patients starting Sativex between January 2014 and February 2015 from the mandatory Italian medicines agency (AIFA) e-registry. Spasticity assessment by the 0-10 numerical rating scale (NRS) scale is available at baseline, after 1â month of treatment (trial period), and at 3 and 6â months. RESULTS: A total of 1615 patients were recruited from 30 MS centres across Italy. After one treatment month (trial period), we found 70.5% of patients reaching a ≥20% improvement (initial response, IR) and 28.2% who had already reached a ≥30% improvement (clinically relevant response, CRR), with a mean NRS score reduction of 22.6% (from 7.5 to 5.8). After a multivariate analysis, we found an increased probability to reach IR at the first month among patients with primary and secondary progressive MS, (n=1169, OR 1.4 95% CI 1.04 to 1.9, p=0.025) and among patients with >8 NRS score at baseline (OR 1.8 95% CI 1.3-2.4 p<0.001). During the 6â months observation period, 631(39.5%) patients discontinued treatment. The main reasons for discontinuation were lack of effectiveness (n=375, 26.2%) and/or adverse events (n=268, 18.7%). CONCLUSIONS: Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.
Assuntos
Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Administração Oral , Canabidiol , Dronabinol , Combinação de Medicamentos , Humanos , Itália , Esclerose Múltipla/complicações , Espasticidade Muscular/etiologia , Extratos Vegetais/administração & dosagem , SegurançaRESUMO
OBJECTIVE: The objective of this paper is to identify clinical or magnetic resonance imaging (MRI) predictors of long-term clinical progression in a large cohort of multiple sclerosis (MS) patients. METHODS: A total of 241 relapsing-remitting (RR) MS patients were included in a nine-year follow-up (FU) study. The reference MRIs were acquired at baseline (BL) as part of a multicenter, cross-sectional, clinical-MRI study. Volumetric MRI metrics were measured by a fully automated, operator-independent, multi-parametric segmentation method. Clinical progression was evaluated as defined by: conversion from RR to secondary progressive (SP) disease course; progression of Expanded Disability Status Scale (EDSS); achievement and time to reach EDSS 4. RESULTS: We concluded that conversion from RR to SP (OR 0.79; CI 0.7-0.9), progression of EDSS (OR 0.85; CI 0.77-0.93), achievement of EDSS 4 (OR 0.8; CI 0.7-0.9), and time to reach EDSS 4 (HR 0.88; CI 0.82-0.94) were all predicted by BL gray matter (GM) volume and, except for progression of EDSS, by BL EDSS (respectively: (OR 2.88; CI 1.9-4.36), (OR 2.7; CI 1.7-4.2), (HR 3.86; CI 1.94-7.70)). CONCLUSIONS: BL GM volume and EDSS are the best long-term predictors of disease progression in RRMS patients with a relatively long and mild disease.
Assuntos
Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/patologia , Adulto , Estudos Transversais , Avaliação da Deficiência , Progressão da Doença , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Neurofilament light chains (NfL) are cytoskeletal biomarkers of axonal damage, about 40-fold higher in cerebrospinal fluid (CSF) compared to serum, and requiring ultrasensitive techniques to be measured in this latter fluid. OBJECTIVES: To compare CSF and serum NfL levels in multiple sclerosis (MS) patients using different platforms. METHODS: 60 newly diagnosed relapsing-remitting MS patients (38 females; median age: 36.5 years, range: 15-60) were enrolled before steroid or disease-modifying treatments. CSF and serum NfL were measured with: the commercial Ella™ microfluidic platform (Bio-Techne), the Lumipulse™ Chemiluminescent Enzyme ImmunoAssay (Fujirebio), and the SIMOA™ on the SR-X instrument using NF-light assays (Quanterix). RESULTS: CSF and serum NfL absolute levels strongly correlated between assays, although being more elevated with Ella™. Passing-Bablok regression showed high agreement in measuring CSF NfL between assays (with greater proportional difference using Ella™), and very high agreement for serum comparing SIMOA™ and Lumipulse™. Similarly, the Bland-Altman comparison evidenced lower biases for Lumipulse™ for both fluids. CONCLUSIONS: CSF and serum NfL in naïve MS patients are reliably measured with all assays. Although not interchangeable, SIMOA™ and Lumipulse™ showed high agreement for serum and CSF values.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Feminino , Humanos , Adulto , Filamentos Intermediários , Biomarcadores , AxôniosRESUMO
BACKGROUND: The earliest detection of progressive multifocal leukoencephalopathy (PML) is crucial in Natalizumab (NTZ)-treated Multiple Sclerosis (MS) patients. This study aims to assess serum Neurofilaments (sNFL) ability to early detect PML in longitudinal patients' follow-up. METHODS: NFL were retrospectively measured in four PML cases occurred at the Regional Referring Center for MS (CRESM, Italy), in samples collected since one year before PML diagnosis, at PML diagnosis, during PML and in post-PML follow-up. sNFL levels were interpreted according to previously defined reference values. Clinical examination and EDSS were performed at each NTZ infusion. Routinary MRI was undertaken every six months; after PML diagnosis, MRI was performed according to clinical evaluation. sNFL were also measured in 45 NTZ-treated patients experiencing NEDA-3 status for at least 12 months. RESULTS: Patients showed different PML onsets and manifestations: in 3 patients routinary brain MRI revealed radiological signs of PML preceding different clinical manifestations, while in one patient brain MRI was performed after the clinical onset. PML diagnosis was defined at the time of the first detection of JCV DNA in cerebrospinal fluid. The following different PML phases were considered: 1. Basal (up to 4 months before PML diagnosis): sNFL values were in the normal range in all patients' samples, except for one (median 9.1 pg/ml, range 6.2-15.1 pg/ml) 2. Pre-PML (within 3 months before PML diagnosis): sNFL were elevated in all available samples (median 19.50 pg/ml, range 15.50-33.80 pg/ml). 3. PML diagnosis: sNFL were elevated in all patients (median 59.20 pg/ml, range 11.1-101.50 pg/ml). 4. PML/IRIS: during this phase, sNFL levels reached their peak (median 96.35 pg/ml, range 20.5-272.9) in all patients. 5. Post-PML (recovery phase, starting from the first MRI without enhancement, up to the end of follow-up): sNFL levels showed a decrease (median 12.80 pg/ml, range 9.30-30.60); however, based on reference values, sNFL were still elevated in 2 out of 4 patients at the end of their follow-up (622 and 887 days after PML diagnosis). sNFL were always elevated when MRI scan suggested a suspicious of PML. In NEDA-3 patients, sNFL levels were in the normal range in all patients' samples (median 4.7 pg/ml, range 1.4-8.6 pg/ml). CONCLUSION: Elevated sNFL were observed not only at PML diagnosis, but also in pre-PML phase. At PML recovery, sNFL weren't normalized in all patients' samples, suggesting ongoing neuronal degeneration. sNFL represent a reliable biomarker and should be introduced in clinical practice as an additional/alternative parameter to MRI to early detect and monitor PML.
Assuntos
Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla , Humanos , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Estudos Retrospectivos , Filamentos Intermediários , Natalizumab/uso terapêutico , BiomarcadoresRESUMO
BACKGROUND AND PURPOSE: Multiple sclerosis (MS) patients are often emotionally disturbed. We investigated anger in these patients in relation to demographic, clinical, and mood characteristics. PATIENTS AND METHODS: About 195 cognitively unimpaired MS patients (150 relapsing-remitting and 45 progressive) were evaluated with the State Trait Anger Expression Inventory, the Chicago Multiscale Depression Inventory, and the State Trait Anxiety Inventory. The patients' anger score distribution was compared with that of the normal Italian population. Correlation coefficients among scale scores were calculated and mean anger scores were compared across different groups of patients by analysis of variance. RESULTS: Of the five different aspects of anger, levels of withheld and controlled Anger were respectively higher and lower than what is expected in the normal population. Although anger was correlated with anxiety and depression, it was largely independent from these mood conditions. Mean anger severity scores were not strongly influenced by individual demographic characteristics and were not higher in more severe patients. CONCLUSIONS: The presence of an altered pattern of anger, unrelated to the clinical severity of MS, suggests that anger is not an emotional reaction to disease stress. An alteration of anger mechanisms might be a direct consequence of the demyelination of the connections among the amygdale, the basal ganglia and the medial prefrontal cortex.
Assuntos
Ira , Esclerose Múltipla/psicologia , Adolescente , Adulto , Idoso , Ansiedade/etiologia , Ansiedade/psicologia , Depressão/etiologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Testes Neuropsicológicos , Adulto JovemRESUMO
Recent studies suggest that in patients with carpal tunnel syndrome, pathological changes occur in the subsynovial connective tissue. Such changes are non-inflammatory synovial fibrosis and vascular proliferation. Thickening of the tendon sheet may cause an increase of canal pressure and damages to the median nerve in the wrist; however, the causes of such events still remain to be clarified. We examined synovial specimens from 26 patients operated on for idiopathic carpal tunnel syndrome. Analysis included histological, ultrastructural and immunohistochemical examination in order to establish a pathological underlying pattern. An explanation for the pathogenesis of the found changes suggested. Our data confirm the presence of a non-inflammatory fibrosis with irregular bundles of collagen. De novo blood vessel formation was also noted. Interestingly the neo-angiogenesis consists of anomalous vessels and may be triggered from various cell types secreting vascular endothelial growth factor (VEGF), including macrophage-like elements similar to endothelial progenitor cells. Therefore, we believe that in the future a non-surgical management of carpal tunnel syndrome might be conjecturable via anti-VEGF drugs.
Assuntos
Síndrome do Túnel Carpal/patologia , Tecido Conjuntivo/patologia , Antígenos CD34/metabolismo , Colágeno/metabolismo , Tecido Conjuntivo/irrigação sanguínea , Tecido Conjuntivo/ultraestrutura , Endotélio Vascular/patologia , Endotélio Vascular/ultraestrutura , Feminino , Fibrose , Humanos , Imuno-Histoquímica , Masculino , Neuropatia Mediana/patologia , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Neovascularização PatológicaRESUMO
BACKGROUND: Teriflunomide (TRF) and Dimethyl fumarate (DMF) are licensed drugs for relapsing-remitting Multiple Sclerosis (RRMS). OBJECTIVES: We aimed to compare the rate and the time to discontinuation among persons with RRMS (pwRRMS), newly treated with TRF and DMF. MATERIALS AND METHODS: A retrospective study on prospectively collected data was performed in nine tertiary MS centers, in Italy. The 24-month discontinuation rate in the two cohorts was the primary study outcome. We also assessed the time to discontinuation and reasons of therapy withdrawn. Discontinuation of TRF and DMF was defined as a gap of treatment ≥ 60 days. RESULTS: A cohort of 903 pwRRMS (316 on TRF and 587 on DMF) was analyzed. During 24 months of follow-up, pwRRMS on TRF and DMF showed similar discontinuation rates. The analysis of predictors with Cox regression model showed differences between the two groups (p for log-rank test = 0.007); male gender [HR 2.21 (1.00-4.90); p = 0.01] and the number of previous switches [HR 1.47 (1.16-1.86); p = 0.01] were associated with higher hazard of discontinuation in the DMF group. CONCLUSIONS: In a real-world setting, pwRRMS on TRF and DMF had similar discontinuation rates over 24 months. Male pwRRMS on DMF with a previous history of therapeutic failure are at more risk of discontinuation therapy.
Assuntos
Crotonatos/administração & dosagem , Fumarato de Dimetilo/administração & dosagem , Imunossupressores/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Toluidinas/administração & dosagem , Adulto , Seguimentos , Humanos , Hidroxibutiratos , Itália , Pessoa de Meia-Idade , Nitrilas , Estudos Retrospectivos , Fatores de TempoRESUMO
Mutations in the Angiogenin gene (ANG) linked to 14q11.2 have been recently discovered to be associated with Amyotrophic Lateral Sclerosis (ALS) in Irish and Scottish populations. In our study we investigated the role of ANG gene in ALS patients from southern Italy. We found a novel mutation in the signal peptide of the ANG gene in a sporadic patient with ALS (SALS). The molecular analysis of the ANG gene also demonstrated an allelic association with the rs11701 single nucleotide polymorphism (SNP) in familial ALS (FALS) but not in SALS patients. Our finding supports the evidence that the ANG gene is involved in ALS.
Assuntos
Esclerose Lateral Amiotrófica/genética , Predisposição Genética para Doença/genética , Neurônios Motores/metabolismo , Mutação/genética , Ribonuclease Pancreático/genética , Adulto , Idoso , Substituição de Aminoácidos/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/fisiopatologia , Mapeamento Cromossômico , Cromossomos Humanos Par 14/genética , Citoproteção/genética , Análise Mutacional de DNA , Feminino , Ligação Genética/genética , Marcadores Genéticos/genética , Testes Genéticos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Neurônios Motores/patologia , Degeneração Neural/genética , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Ribonuclease Pancreático/químicaRESUMO
Multiple sclerosis (MS) is a common, heterogeneous disorder of the central nervous system with a complex trait composed of both genetic and environmental factors. Recently, scientific interest has increased in defining factors that possibly contribute to brain functional plasticity; the results might be useful to assess the relationship between MS lesion burden and clinical events, as well as explaining the well-known phenotypic heterogeneity of the disease. In this study, we explored the effect of the Val66Met brain-derived neurotrophic factor (BDNF) functional polymorphism on cognitive performances and volumetric measurements obtained by magnetic resonance imaging of the brain in a selected population of relapsing-remitting MS (RRMS) patients, with relatively short disease duration and minimal clinical disability, compared to gender, age and educational-level matched healthy subjects. We found that in the RRMS group, the BDNF Met-allele was significantly associated with the lower volume of cerebral grey matter (GM) (P = 0.005). Furthermore, a significant (P = 0.013) interaction effect between 'MS-status' and the BDNF genotype was found for GM volumes, with the result that patients carrying the BDNF Met-allele showed a higher risk of developing global GM atrophy than the homozygous Val/Val. No BDNF-related impact on global neuropsychological functions resulted in either RRMS patients or controls. Our data seem to be consistent with the reported influence of BDNF in neuronal plasticity, thus suggesting that the Met-allele might have a negative prognostic effect on cortical morphometry in RRMS patients.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Córtex Cerebral/patologia , Esclerose Múltipla Recidivante-Remitente/genética , Adolescente , Adulto , Atrofia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Estudos de Casos e Controles , Córtex Cerebral/metabolismo , Estudos Transversais , Feminino , Frequência do Gene , Humanos , Masculino , Análise por Pareamento , Esclerose Múltipla Recidivante-Remitente/metabolismo , Esclerose Múltipla Recidivante-Remitente/patologia , Neurônios/metabolismo , Neurônios/patologia , Tamanho do Órgão , Polimorfismo de Nucleotídeo Único/fisiologia , Valores de ReferênciaRESUMO
Lymphocyte and monocyte brain infiltration determines inflammation in multiple sclerosis. The trafficking of these cells into the CNS results from the VLA-4 binding with its ligand on brain endothelial cells. MS patients treated with an antibody against the alpha-4 subunit, which inhibits this interaction, prevents brain lesion development. We investigated the association between VLA-4 gene polymorphisms and MS in a study on 275 patients and 255 controls. No differences were detected, thus suggesting that these polymorphisms are not a significant genetic risk factor for susceptibility to MS in Italy.
Assuntos
Predisposição Genética para Doença , Integrina alfa4beta1/genética , Esclerose Múltipla/genética , Polimorfismo Genético/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to beta-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS.
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Transtornos Cognitivos/complicações , Transtornos Cognitivos/fisiopatologia , Variação Genética/genética , Esclerose Múltipla/complicações , Esclerose Múltipla/genética , Peroxidase/genética , Alelos , Transtornos Cognitivos/genética , Frequência do Gene , Genótipo , Humanos , Esclerose Múltipla/enzimologia , Esclerose Múltipla/fisiopatologia , Polimorfismo GenéticoRESUMO
Multiple Sclerosis (MS) is a heterogeneous disease and a variable percentage of patients are non-responders to common treatment. Early diagnosis of non-responders allows change to a more useful therapy for the patient and better allocates a large amount of financial resources. Quantification of Neutralizing antibodies (Nabs) and of biological activity of IFN-ß are recognized approaches to identify immuno-pharmacological non-responders. A consistent number of studies have demonstrated that quantification of Myxovirus-induced protein A (MxA) is a valid biomarker to detect immune-pharmacological non responders after one year of treatment. Persistent high titre of Nabs and absence of biological activity predict abolition of IFN-ß effects in disease activity measured through MRI, number of relapses and disability. Guidelines and flow-charts including both Nabs and MxA quantification are presented.
Assuntos
Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Anticorpos Neutralizantes/sangue , Biomarcadores/análise , Humanos , Proteínas de Resistência a Myxovirus/análise , Proteínas de Resistência a Myxovirus/genética , RNA Mensageiro/análise , RNA Mensageiro/genéticaRESUMO
A 64-year-old woman, who had no personal or family history of neurologic diseases, had an 18-month history of epilepsia partialis continua (EPC) associated with a moderate intellectual deterioration and subtle extrapyramidal rigidity. There was no photosensitive response. A thorough laboratory investigation was unremarkable. A biopsy of the rectal mucosa revealed abundant fingerprint profiles diagnostic of Kufs' disease (KD). Our case expands the clinical picture of KD and suggests that such a diagnosis should be considered in adult-onset EPC.
Assuntos
Epilepsia Parcial Contínua/diagnóstico , Lipofuscinoses Ceroides Neuronais/diagnóstico , Idade de Início , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Músculo Liso/patologia , Lipofuscinoses Ceroides Neuronais/patologiaRESUMO
OBJECTIVE: To assess the efficacy of two different high doses of intravenous methylprednisolone (IVMP) for the treatment of relapses in MS. BACKGROUND: IVMP is the treatment of choice for MS relapses, but it is unknown whether its effects are dose related. METHODS: We conducted a double-blind, randomized study. Follow-up included serial clinical and MRI recordings at baseline and at 7, 15, 30, and 60 days after the beginning of treatment. Outcome measures were the number of brain and cervical spinal cord MRI contrast-enhancing lesions, and the Expanded Disability Status Scale score. RESULTS: Both treatment regimens improved clinical scores and reduced the number of MRI enhancing lesions during the follow-up period. The higher dose of IVMP was significantly more effective than the lower dose in reducing the number of MRI contrast-enhanced lesions at 30 and 60 days, mainly by decreasing the rate of new lesion formation. CONCLUSIONS: The higher dosage of IVMP has a more powerful and prolonged action in maintaining blood-brain barrier integrity after a clinical relapse.
Assuntos
Metilprednisolona/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Adulto , Encéfalo/patologia , Avaliação da Deficiência , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/fisiopatologia , Pescoço , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/efeitos adversos , Recidiva , Medula Espinal/patologiaRESUMO
A 9-year-old girl, who had no family history of neurologic diseases in the first-degree relatives, had a 3-year history of progressive myoclonus epilepsy (PME). A thorough laboratory investigation was normal. As two sisters of her paternal grandmother were said to have Huntington's disease (HD), the authors looked for HD and found a CAG repeat expansion of 115 repeats. This diagnosis should be considered in addition to other causes in patients with PME. Moreover, the current case further supports the notion that HD should be considered even when a family history is not obvious.
Assuntos
Doença de Huntington/diagnóstico , Epilepsias Mioclônicas Progressivas/diagnóstico , Criança , Eletroencefalografia , Feminino , Humanos , Doença de Huntington/genética , Doença de Huntington/fisiopatologia , Epilepsias Mioclônicas Progressivas/fisiopatologiaRESUMO
BACKGROUND: There is evidence that patients with chronic daily headache (CDH) may have isolated intracranial hypertension without papilledema (IHWOP). Recent studies have emphasized that isolated IH may be due to cerebral venous thrombosis (CVT). OBJECTIVE: To detect the occurrence of CVT in patients with CDH. METHODS: The authors investigated the occurrence of CVT in 114 consecutive patients with CDH by using MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 28 age-matched control subjects. RESULTS: In all the control subjects, both MRV and CSF pressure were normal. One hundred three of the 114 patients with CDH had normal MRV. Twenty-seven (Group 1) of these 103 patients underwent LP, and all of them had normal CSF pressure. Eleven (9.6%) of the 114 patients with CDH had CVT of one or both transverse sinuses. Six of these 11 patients had flowing abnormalities of one transverse sinus (Group 2), whereas the remaining five patients showed involvement of both transverse sinuses (Group 3). The CSF pressure of Group 2 was higher than that of either Group 1 or the control subjects, and one of the six patients showed isolated IHWOP. Patients of Group 3 displayed the highest CSF pressure, and four of five had isolated IHWOP. The headache profiles of patients with CDH and CVT did not differ from those of patients with CDH but normal MRV. CONCLUSIONS: CVT, as detected by MRV, occurred in 9.6% of patients who presented with CDH. Almost half of the patients with CVT had isolated IHWOP. These results suggest that MRV may be a useful tool for selecting patients with CDH who should have LP to exclude isolated IHWOP.
Assuntos
Veias Cerebrais , Ritmo Circadiano , Cefaleia/complicações , Hipertensão Intracraniana/complicações , Trombose Venosa/complicações , Adulto , Pressão do Líquido Cefalorraquidiano , Doença Crônica , Feminino , Humanos , Hipertensão Intracraniana/diagnóstico , Hipertensão Intracraniana/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Papiledema/complicações , Flebografia/métodos , Punção Espinal , Trombose Venosa/diagnósticoRESUMO
BACKGROUND: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by mutations in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) gene, mapping on chromosome 20q13.2. A second ADNFLE locus was mapped on chromosome 15q24. OBJECTIVE: To report a new third ADNFLE locus on chromosome 1 in a large Italian family. METHODS: The authors performed a clinical and genetic study in a large, three-generation ADNFLE family from southern Italy, including eight affected individuals and three obligate carriers. RESULTS: The age at onset of seizures was around 9 years of age and all affected individuals manifested nocturnal partial seizures of frontal lobe origin. Interictal awake and sleep EEG recordings showed no definite epileptiform abnormalities in most patients. Ictal video-EEG showed that the attacks were partial seizures with a frontal lobe semiology. Intellectual and neurologic examinations, and brain CT or MRI results were always normal. Carbamazepine was effective in all treated patients. Exclusion mapping of the known loci linked to ADNFLE-ENFL1, and ENFL2, on chromosomes 20q13.2 and 15q24-was performed on the pedigree before starting the genome-wide linkage analysis. The whole genome scan mapping allowed the identification of a new ADNFLE locus spanning the pericentromeric region of chromosome 1. CONCLUSIONS: The authors provided evidence for a third locus associated to autosomal dominant nocturnal frontal lobe epilepsy on chromosome 1. Among the known genes mapping within this critical region, the ss2 subunit of the nicotinic receptor (CHRNB2) represents the most obvious candidate.