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2.
Eur J Neurol ; 16(6): 771-4, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19236470

RESUMO

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS. METHODS: We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients. RESULTS: MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = -0.407; P = 0.075). CONCLUSIONS: We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Quimiocinas/análise , Inflamação/diagnóstico , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Quimiocina CCL2/análise , Quimiocina CCL2/sangue , Quimiocina CCL2/líquido cefalorraquidiano , Quimiocinas/sangue , Quimiocinas/líquido cefalorraquidiano , Progressão da Doença , Diagnóstico Precoce , Gliose/sangue , Gliose/líquido cefalorraquidiano , Gliose/diagnóstico , Humanos , Inflamação/sangue , Inflamação/líquido cefalorraquidiano , Interleucina-8/análise , Interleucina-8/sangue , Interleucina-8/líquido cefalorraquidiano , Microglia/imunologia , Microglia/metabolismo , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade , Fatores de Tempo , Regulação para Cima/imunologia
3.
J Neurol ; 255(1): 77-88, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18204807

RESUMO

Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migraine-like headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy. No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drugs.


Assuntos
Doenças Arteriais Cerebrais/patologia , Nefropatias/patologia , Hepatopatias/patologia , Doenças Retinianas/patologia , Doenças Vasculares/patologia , Adulto , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Calcinose/patologia , Calcinose/fisiopatologia , Doenças Arteriais Cerebrais/fisiopatologia , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Imunossupressores/uso terapêutico , Nefropatias/fisiopatologia , Hepatopatias/fisiopatologia , Falência Hepática/patologia , Falência Hepática/fisiopatologia , Masculino , Microcirculação/patologia , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologia , Artéria Retiniana/patologia , Artéria Retiniana/fisiopatologia , Doenças Retinianas/fisiopatologia , Síndrome , Resultado do Tratamento , Doenças Vasculares/fisiopatologia , Vasculite/patologia , Vasculite/fisiopatologia , Vísceras/irrigação sanguínea , Vísceras/patologia , Vísceras/fisiopatologia
9.
AJNR Am J Neuroradiol ; 27(6): 1272-4, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16775278

RESUMO

Palatal tremor (PT), also known as palatal myoclonus, is defined by short rhythmic contractions of the palatal musculature. Functional MR imaging (fMRI) revealed prominent bilateral neuronal activation in the putamen associated with essential palatal tremor (EPT) in a 41-year-old man. This implies a central role of the putamen in EPT, most likely as a consequence of diminished inhibition in an afferent pathway. Because fMRI primarily detects activations, dysfunctional areas remain obscure. The present functional study complements previous pathologic studies, which associated PT with lesions to dentate nucleus, red nucleus, and the inferior olive (Guillain-Mollaret triangle).


Assuntos
Mapeamento Encefálico , Tremor Essencial/fisiopatologia , Imageamento por Ressonância Magnética , Músculos Palatinos/fisiopatologia , Putamen/fisiopatologia , Adulto , Vias Aferentes , Humanos , Masculino , Contração Muscular , Músculos do Pescoço/fisiopatologia
10.
Neurology ; 66(5): 742-4, 2006 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-16534115

RESUMO

Rituximab has been administered successfully in patients with polyneuropathy associated with antibodies to myelin-associated glycoprotein (anti-MAG). The authors present a follow-up study with high-dose rituximab. Increase of rituximab from 375 mg/m2 to a dose of 750 mg/m2 was well tolerated and led to clinical improvement in four of eight patients, along with improvement of nerve conduction velocities and a reduction of anti-MAG antibody titers.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos/uso terapêutico , Glicoproteína Associada a Mielina/imunologia , Polineuropatias/tratamento farmacológico , Polineuropatias/imunologia , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Citotoxicidade Celular Dependente de Anticorpos , Linfócitos B/imunologia , Feminino , Seguimentos , Humanos , Imunoglobulina M/sangue , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Rituximab , Fatores de Tempo
11.
Praxis (Bern 1994) ; 95(8): 263-8, 269-71, 2006 Feb 22.
Artigo em Alemão | MEDLINE | ID: mdl-16523990

RESUMO

Although disease-specific treatment of amyotrophic lateral sclerosis is still unsatisfactory, a number of advances have been made in the symptomatic therapy of ALS patients within the last decade. Current data suggest that active and aggressive multidisciplinary management of ALS patients improve their quality of life and prolong their survival. Patient and caregiver communications and decisions are increasingly recognized to be a relevant part of this management. A wide range of supportive and palliative measures, in particular the widely use of symptomatic drugs for pseudobulbar affect, sialorrhea, and sleep disorders is available to relieve patients symptomatology. In addition, patients quality of life has been profoundly improved by the introduction of enteral nutrition and non-invasive ventilation.


Assuntos
Doença dos Neurônios Motores/terapia , Cuidados Paliativos , Progressão da Doença , Humanos , Doença dos Neurônios Motores/diagnóstico , Doença dos Neurônios Motores/psicologia , Cuidados Paliativos/psicologia , Equipe de Assistência ao Paciente , Qualidade de Vida/psicologia , Assistência Terminal/psicologia
12.
Mult Scler ; 12(6): 814-23, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17263012

RESUMO

Over the last decade, hematopoietic stem cells transplantation (HSCT) has been increasingly used in the treatment of severe progressive autoimmune diseases. We report a retrospective survey of 183 multiple sclerosis (MS) patients, recorded in the database of the European Blood and Marrow Transplantation Group (EBMT). Transplant data were available from 178 patients who received an autologous graft. Overall, transplant related mortality (TRM) was 5.3% and was restricted to the period 1995-2000, with no further TRM reported since then. Busulphan-based regimens were significantly associated with TRM. Clinical status at the time of transplant and transplant techniques showed some correlations with toxicity. No toxic deaths were reported among the 53 patients treated with the BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan)/antithymocyte globulin (ATG) regimen without graft manipulation, irrespective of their clinical condition at the time of the transplant. Improvement or stabilization of neurological conditions occurred in 63% of patients at a median follow-up of 41.7 months, and was not associated with the intensity of the conditioning regimen. In this large series, HSCT was shown as a promising procedure to slow down progression in a subset of patients affected by severe, progressive MS; the safety and feasibility of the procedure can be significantly improved by appropriate patient selection and choice of transplant regimen.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Esclerose Múltipla Crônica Progressiva/mortalidade , Esclerose Múltipla Crônica Progressiva/terapia , Adolescente , Adulto , Bases de Dados Factuais , Avaliação da Deficiência , Progressão da Doença , Europa (Continente) , Feminino , Seguimentos , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo
13.
J Neurol ; 252(10): 1167-70, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16184341

RESUMO

BACKGROUND: Orolingual angioedema can occur during thrombolysis with alteplase in stroke patients. However, data about its frequency, severity and the significance of concurrent use of angiotensin-converting-enzyme inhibitors (ACEi) are sparse. OBJECTIVE: (1), to alert to the potentially life-threatening complication of orolingual angioedema. (2), to present CT-scans of the tongue which exclude lingual hematoma. (3), to estimate the frequency of orolingual angioedema. (4), to evaluate the risk associated with the concurrent use of ACEi. METHODS: Single center, databank-based observational study on 120 consecutive patients with i. v. alteplase for acute stroke. Meta-analysis of all stroke studies on alteplase-associated angioedema, which provided detailed information about the use of ACE-inhibitors. Across studies, the Peto odds ratio of orolingual angioedema for "concurrent use of ACEi" was calculated. RESULTS: Orolingual angioedema occurred in 2 of 120 patients (1.7%, 95% CI 0.2-5.9 %). Angioedema was mild in one, but rapidly progressive in another patient. Impending asphyxia prompted immediate intubation. CT showed orolingual swelling but no bleeding. One of 19 (5%) patients taking ACEi had orolingual angioedema, compared to 1 of 101 (1%) patients without ACEi. Medline search identified one further study about the occurrence of alteplase-associated angioedema in stroke patients stratified to the use of ACEi. Peto odds ratio of 37 (95 % CI 8-171) indicated an increased risk of alteplasetriggered angioedema for patients with ACEi (p <0.001). CONCLUSION: Orolingual angioedema is a potentially life-threatening complication of alteplase treatment in stroke patients, especially in those with ACEi. Orolingual hematoma as differential diagnosis can be excluded by CT-scan.


Assuntos
Angioedema/etiologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Angioedema/induzido quimicamente , Angioedema/epidemiologia , Angioedema/patologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Isquemia Encefálica/complicações , Intervalos de Confiança , Sinergismo Farmacológico , Humanos , Incidência , Pessoa de Meia-Idade , Boca/patologia , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Fatores de Tempo , Ativador de Plasminogênio Tecidual/uso terapêutico , Tomografia Computadorizada por Raios X , Língua/patologia
14.
J Neurol ; 252(11): 1387-93, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15942704

RESUMO

OBJECTIVE: In acute ischemic stroke, the number and distribution of lesions on diffusion weighted imaging (DWI) have been shown to give clues to the underlying pathogenetic mechanisms. The objective of this study was to determine whether lesion features on DWI differ between stroke due to large artery atherosclerosis (LAA) and cardioembolism (CE), and to assess the role of apparent diffusion coefficient maps (ADC). METHODS: We retrospectively studied 83 consecutive patients with stroke caused by either LAA (n=40) or cardioembolism (n=43). DWI lesions were characterized by number, size, distribution (i. e. lesion pattern) and signal intensity on ADC maps. In part A, all hyperintense DWI lesions regardless of their ADC were compared. In part B, only hyperintense DWI lesions with hypointense appearance on ADC maps (i. e. acute lesions) were assessed. RESULTS: Part A: The frequency of multiple hyperintense DWI lesions (LAA: 28/40, CE: 21/43; p< 0.05) and the lesion number (LAA 4.7+/- 4.9; CE: 3.1+/- 4.7; p=0.01) were higher in LAA-patients. Involvement of >1 circulation (i. e. anterior plus posterior or bilateral anterior circulations) was present in 5 LAA-patients (13 %) and 4 CE-patients (9 %). Lesion size did not differ between LAA-stroke (35.1+/- 33.7 mm) and CE-stroke (35.4+/- 27.8 mm). Part B: Multiple hyperintense DWI lesions with low ADC occurred in 23/40 LAA-patients and in 15/43 CE-patients (p<0.05). Lesions in >1 circulation occurred only in CE-stroke (n=3; 7%) and never in LAA-stroke. CONCLUSIONS: (1) Multiple ischemic lesions occur significantly more often in LAA-stroke than in CE-stroke. (2) ADC maps are important in the comparison of DWI lesion patterns; DWI lesions in >1 circulation can only be assigned to a cardioembolic etiology if they appear hypointense on ADC maps.


Assuntos
Imagem de Difusão por Ressonância Magnética , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Idoso , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Embolia/complicações , Embolia/diagnóstico por imagem , Embolia/patologia , Feminino , Cardiopatias/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Acidente Vascular Cerebral/patologia
17.
Eur J Neurol ; 11(8): 567-8, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15272904

RESUMO

We describe a case of a 65-year old patient diagnosed with amyotrophic lateral sclerosis. The clinical findings, with symmetric, predominantly proximal wasting and weakness of both arms (especially of the infra-, supraspinatus and deltoideus) leading to severe functional disability and contrasting with preserved independent ambulation and sparing of bulbar muscles, were consistent with the proposed criteria of the so-called flail arm syndrome. Based on our case we characterize the clinical features of flail arm syndrome and review the literature.


Assuntos
Esclerose Lateral Amiotrófica/complicações , Braço/fisiopatologia , Pessoas com Deficiência , Idoso , Esclerose Lateral Amiotrófica/classificação , Humanos , Masculino
18.
Neurology ; 62(4): 574-80, 2004 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-14981173

RESUMO

OBJECTIVE: To study the association between diffusion-weighted imaging (DWI) characteristics and stroke etiology, stroke severity, and functional outcome in patients with infratentorial strokes. METHODS: The authors prospectively studied 22 consecutive patients with acute infratentorial strokes. They used a blinded comparison of DWI features (number, distribution, and volume of lesions) with clinical characteristics, namely, stroke etiology (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] classification), severity (NIH Stroke Scale [NIHSS]), length of stay (LOS), and functional 3-month outcome using modified Rankin Scale, Barthel Index, and a dichotomized outcome status (living at home vs institutionalization or death). RESULTS: Acute infratentorial DWI lesions were detected in 95% (21/22) of the patients. The number (p = 0.01) and the distribution (p < 0.001) of DWI lesions were correlated with stroke etiology. Patients with cardioembolic strokes (n = 5) had more DWI lesions (8.0 +/- 6.0) than those with other stroke etiologies (n = 17; 1.3 +/- 0.9; p < 0.001). Their lesion distribution differed from that of patients with noncardioembolic strokes (p < 0.001). Clinically silent, acute DWI lesions in the anterior circulation in addition to their infratentorial lesions were visualized in 3 of 5 patients with cardioembolic stroke and in none of 17 patients without sources of cardioembolism (p < 0.001). Pure infratentorial lesions were present in 15 of 17 patients with noncardioembolic strokes and in none of 5 cardioembolic stroke patients (p < 0.001). DWI lesion volume was not correlated with NIHSS score, LOS, outcome scores, or outcome status. CONCLUSION: In infratentorial strokes, multiple DWI lesions and a distribution of subsidiary, clinically silent DWI lesions in the anterior circulation suggest a cardioembolic stroke etiology. However, DWI lesion volume did not correlate with the NIHSS score and was no predictor of outcome.


Assuntos
Imageamento por Ressonância Magnética/métodos , Acidente Vascular Cerebral/patologia , Adulto , Idoso , Dano Encefálico Crônico/epidemiologia , Dano Encefálico Crônico/etiologia , Cerebelo/irrigação sanguínea , Feminino , Cardiopatias/complicações , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/patologia , Embolia Intracraniana/etiologia , Embolia Intracraniana/patologia , Tempo de Internação , Masculino , Mesencéfalo/irrigação sanguínea , Pessoa de Meia-Idade , Ponte/irrigação sanguínea , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do Tratamento
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