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1.
Neurology ; 97(7): e706-e719, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34400568

RESUMO

OBJECTIVE: To determine similarities and differences in key predictors of recovery of bimanual hand use and unimanual motor impairment after stroke. METHOD: In this prospective longitudinal study, 89 patients with first-ever stroke with arm paresis were assessed at 3 weeks and 3 and 6 months after stroke onset. Bimanual activity performance was assessed with the Adult Assisting Hand Assessment Stroke (Ad-AHA), and unimanual motor impairment was assessed with the Fugl-Meyer Assessment (FMA). Candidate predictors included shoulder abduction and finger extension measured by the corresponding FMA items (FMA-SAFE; range 0-4) and sensory and cognitive impairment. MRI was used to measure weighted corticospinal tract lesion load (wCST-LL) and resting-state interhemispheric functional connectivity (FC). RESULTS: Initial Ad-AHA performance was poor but improved over time in all (mild-severe) impairment subgroups. Ad-AHA correlated with FMA at each time point (r > 0.88, p < 0.001), and recovery trajectories were similar. In patients with moderate to severe initial FMA, FMA-SAFE score was the strongest predictor of Ad-AHA outcome (R 2 = 0.81) and degree of recovery (R 2 = 0.64). Two-point discrimination explained additional variance in Ad-AHA outcome (R 2 = 0.05). Repeated analyses without FMA-SAFE score identified wCST-LL and cognitive impairment as additional predictors. A wCST-LL >5.5 cm3 strongly predicted low to minimal FMA/Ad-AHA recovery (≤10 and 20 points respectively, specificity = 0.91). FC explained some additional variance to FMA-SAFE score only in unimanual recovery. CONCLUSION: Although recovery of bimanual activity depends on the extent of corticospinal tract injury and initial sensory and cognitive impairments, FMA-SAFE score captures most of the variance explained by these mechanisms. FMA-SAFE score, a straightforward clinical measure, strongly predicts bimanual recovery. CLINICALTRIALSGOV IDENTIFIER: NCT02878304. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the FMA-SAFE score predicts bimanual recovery after stroke.


Assuntos
Disfunção Cognitiva/fisiopatologia , Conectoma , Mãos/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Paresia/fisiopatologia , Desempenho Psicomotor/fisiologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paresia/diagnóstico , Paresia/etiologia , Prognóstico , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico
2.
Front Neurol ; 10: 836, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456734

RESUMO

Objective: This longitudinal observational study investigated how neural stretch-resistance in wrist and finger flexors develops after stroke and relates to motor recovery, secondary complications, and lesion location. Methods: Sixty-one patients were assessed at 3 weeks (T1), three (T2), and 6 months (T3) after stroke using the NeuroFlexor method and clinical tests. Magnetic Resonance Imaging was used to calculate weighted corticospinal tract lesion load (wCST-LL) and to perform voxel-based lesion symptom mapping. Results: NeuroFlexor assessment demonstrated spasticity (neural component [NC] >3.4N normative cut-off) in 33% of patients at T1 and in 51% at T3. Four subgroups were identified: early Severe spasticity (n = 10), early Moderate spasticity (n = 10), Late developing spasticity (n = 17) and No spasticity (n = 24). All except the Severe spasticity group improved significantly in Fugl-Meyer Assessment (FMA-HAND) to T3. The Severe and Late spasticity groups did not improve in Box and Blocks Test. The Severe spasticity group showed a 25° reduction in passive range of movement and more frequent arm pain at T3. wCST-LL correlated positively with NC at T1 and T3, even after controlling for FMA-HAND and lesion volume. Voxel-based lesion symptom mapping showed that lesioned white matter below cortical hand knob correlated positively with NC. Conclusion: Severe hand spasticity early after stroke is negatively associated with hand motor recovery and positively associated with the development of secondary complications. Corticospinal tract damage predicts development of spasticity. Early quantitative hand spasticity measurement may have potential to predict motor recovery and could guide targeted rehabilitation interventions after stroke.

3.
Acta Orthop ; 88(2): 145-151, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27967333

RESUMO

Background and purpose - Total hip replacement (THR) is the preferred method for the active and lucid elderly patient with a displaced femoral neck fracture (FNF). Controversy still exists regarding the use of cemented or uncemented stems in these patients. We compared the effectiveness and safety between a modern cemented, and a modern uncemented hydroxyapatite-coated femoral stem in patients 65-79 years of age who were treated with THR for displaced FNF. Patients and methods - In a single-center, single-blinded randomized controlled trial, we included 69 patients, mean age 75 (65-79) and with a displaced FNF (Garden III-IV). 35 patients were randomized to a cemented THR and 34 to a reverse-hybrid THR with an uncemented stem. Primary endpoints were: prevalence of all hip-related complications and health-related quality of life, evaluated with EuroQol-5D (EQ-5D) index up to 2 years after surgery. Secondary outcomes included: overall mortality, general medical complications, and hip function. The patients were followed up at 3, 12, and 24 months. Results - According to the calculation of sample size, 140 patients would be required for the primary endpoints, but the study was stopped when only half of the sample size was included (n = 69). An interim analysis at that time showed that the total number of early hip-related complications was substantially higher in the uncemented group, 9 (among them, 3 dislocations and 4 periprosthetic fractures) as compared to 1 in the cemented group. The mortality and functional outcome scores were similar in the 2 groups. Interpretation - We do not recommend uncemented femoral stems for the treatment of elderly patients with displaced FNFs.


Assuntos
Artroplastia de Quadril/métodos , Cimentação/estatística & dados numéricos , Fraturas do Colo Femoral/cirurgia , Nível de Saúde , Luxação do Quadril/epidemiologia , Prótese de Quadril , Fraturas Periprotéticas/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Idoso , Feminino , Humanos , Masculino , Desenho de Prótese , Método Simples-Cego , Resultado do Tratamento
5.
J Stroke Cerebrovasc Dis ; 24(10): 2348-57, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26303791

RESUMO

BACKGROUND: The objective of this study was to compare nonresponders (NR) and responders (R) to clopidogrel with respect to presence of microvascular and macrovascular pathology in a cohort of patients with recent minor ischemic stroke (IS) or transient ischemic attack (TIA). METHODS: Seventy-two patients treated with clopidogrel after IS or TIA were evaluated 1 month after onset. Platelet aggregation was measured by multiple electrode aggregometry (Multiplate). Nonresponse was defined according to recent consensus. The degree of cerebral small-vessel disease (cSVD) was evaluated on computed tomography scans of the brain using Fazekas scale for white matter changes. Carotid atherosclerosis was evaluated by ultrasound or computed tomography/magnetic resonance angiography. RESULTS: Twenty-two percent of patients were NR. Moderate to extensive cSVD was more common for NR than R, 56% versus 25%, odds ratio 3.9 (1.2-12), P = .03. Correspondingly, 39% of patients with cSVD were NR versus 14% of patients with no or mild cSVD. No differences were found between NR and R in prevalence or severity of carotid atherosclerosis. NR had higher platelet aggregation response than R after stimulation with arachidonic acid or thrombin receptor-activating peptide, indicating a general platelet hyperreactivity. In a univariate analysis, hypertension, previous IS, glucose intolerance, pulse pressure above median, and presence of moderate to extensive cSVD were associated with the NR phenotype. CONCLUSIONS: Nonresponsiveness to clopidogrel after minor IS or TIA is associated with radiological cSVD but not with carotid atherosclerosis. PRACTICE/IMPLICATIONS: Measurement of platelet function is warranted in patients with cSVD. Larger studies on alternative or tailored antiplatelet treatment for these patients should be initiated.


Assuntos
Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Ataque Isquêmico Transitório/metabolismo , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Ticlopidina/análogos & derivados , Idoso , Glicemia , Doenças das Artérias Carótidas , Doenças de Pequenos Vasos Cerebrais/diagnóstico , Clopidogrel , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Ataque Isquêmico Transitório/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neuroimagem , Agregação Plaquetária , Radiografia , Estatísticas não Paramétricas , Suécia , Ticlopidina/efeitos adversos , Ultrassonografia
6.
Horm Res Paediatr ; 75(5): 354-61, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21304249

RESUMO

BACKGROUND/AIMS: Pamidronate is widely used to treat pediatric patients with osteogenesis imperfecta (OI). We aimed at delineating the effects of monthly pamidronate therapy on the growth of different body segments in prepubertal OI patients. METHODS: The study included 14 prepubertal patients (12 boys, 2 girls) with mild forms of OI (type I and IV). The mean age at treatment start was 7:8 years:months (3:7-11:0). Pamidronate was given as monthly intravenous infusions. The patients were measured 1 year before, at treatment start and 1 and 2 years after treatment start. RESULTS: Height standard deviation score (SDS) and sitting height SDS significantly increased (p < 0.05) during the first year of treatment when compared to the pre-treatment year. No further improvement was detected during the second year of treatment. However, when plotted on disease-specific growth charts (untreated patients with the same OI types), height gain was significant during the first (p < 0.001) and second (p < 0.05) years of treatment. All patients increased their bone mineral density throughout the follow-up. CONCLUSION: Monthly pamidronate improves the growth of prepubertal patients with mild OI, where the most prominent growth stimulation is seen in the upper body segment.


Assuntos
Difosfonatos/administração & dosagem , Osteogênese Imperfeita/tratamento farmacológico , Constituição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/administração & dosagem , Desenvolvimento Ósseo/efeitos dos fármacos , Desenvolvimento Ósseo/fisiologia , Osso e Ossos/efeitos dos fármacos , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Humanos , Injeções Intravenosas , Masculino , Pamidronato , Puberdade/efeitos dos fármacos , Puberdade/fisiologia , Resultado do Tratamento
7.
Pediatr Blood Cancer ; 56(2): 250-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21157893

RESUMO

BACKGROUND: Patients with Langerhans cell histiocytosis (LCH) may develop neurodegeneration and other central nervous system (CNS) dysfunctions revealed by brain magnetic resonance imaging (MRI). We estimated the incidence and pattern of pathological brain MRI findings in a well-defined, population-based cohort of children with LCH. METHODS: Among children under 15 years of age diagnosed with LCH in the Stockholm County during 1992-2001, brain MRI was performed at a single center in children with clinical and/or laboratory signs of CNS involvement, including endocrine dysfunction. RESULTS: Out of the 29 children (16 males, 13 females) diagnosed with LCH, brain MRI was performed based on clinical indications in 16 children (55%) with either abnormal endocrine findings (n = 6), such as diabetes insipidus (n = 5), low IGF-1 (n = 1), or panhypopituitarism (n = 1), or clinical CNS symptoms (n = 10). CNS MRI abnormalities were demonstrated in eight children (28%), at a median time of 3.5 years after LCH diagnosis (range 1-11.4 years). Altogether 7 of the 29 children (24%) had MRI findings associated with neurodegeneration, corresponding to a minimal incidence of 2.1/10(6) children per year. Neurodegenerative abnormalities tended to be more frequent in patients with craniofacial involvement (P = 0.12). CONCLUSIONS: The minimal annual incidence rate of neurodegenerative associated radiographic findings in LCH is estimated at 2.1/10(6) children (24% of all children with LCH). An important question is whether all patients with LCH, or certain forms of LCH, should be recommended for a late follow-up examination including MRI. In patients with CNS-LCH, neurological, neuropsychological, neurophysiological, neurochemical and neuroradiological follow-up assessment is suggested.


Assuntos
Doenças do Sistema Nervoso Central/epidemiologia , Doenças do Sistema Nervoso Central/patologia , Histiocitose de Células de Langerhans/epidemiologia , Histiocitose de Células de Langerhans/patologia , Encéfalo/patologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Imageamento por Ressonância Magnética , Masculino
8.
Acta Paediatr ; 100(7): e36-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21166862

RESUMO

AIM: There is currently no well-accepted therapy for central nervous system Langerhans cell histiocytosis (CNS-LCH), a neuroinflammatory disease clinically characterized by often progressive, neurological symptoms including ataxia, dysarthria, dysphagia, hypertonicity, intellectual impairment and behavioural abnormalities. We applied immunomodulative/anti-inflammatory treatment on a patient with progressive CNS-LCH disease. METHOD: Intravenous immunoglobulin (IVIG) was administered monthly for 15 years to a patient with severe, image-verified neurodegenerative CNS-LCH. RESULTS: During the IVIG treatment, the neurological deterioration initially appeared to be haltered, but over time there was still some deterioration. CONCLUSIONS: IVIG may be beneficial in partly haltering CNS-LCH neurodegeneration, but further studies are needed.


Assuntos
Doenças do Sistema Nervoso Central/tratamento farmacológico , Histiocitose de Células de Langerhans/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Seguimentos , Humanos , Lactente , Masculino , Fatores de Tempo , Resultado do Tratamento
9.
Pediatr Blood Cancer ; 53(7): 1264-70, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19688833

RESUMO

BACKGROUND: Progressive neurodegeneration may result in potentially severe cognitive and motor dysfunctions as a complication of Langerhans cell histiocytosis (LCH), a suggested IL-17A-associated inflammatory condition. To detect this complication (CNS-LCH) early and to evaluate the potential efficacy of therapeutic interventions, biomarkers detecting and measuring ongoing neurodegeneration would be valuable. We evaluated cerebrospinal fluid (CSF) biomarkers of ongoing neurodegeneration in CNS-LCH patients. PROCEDURE: Nine patients with endocrine, neuromotor, cognitive or/and behavioral abnormalities as well as neuroradiological evidence of CNS-LCH were evaluated 4-12 years after LCH diagnosis for CSF levels of neurofilament protein light chain (NF-L), glial fibrillary acid protein (GFAp), and total tau protein (TAU). Two patients were analyzed longitudinally. One hundred ten children with newly diagnosed acute lymphoblastic leukemia (ALL) served as controls. RESULTS: NF-L, TAU, and GFAp levels were elevated in four, six, and eight of nine patients studied, respectively. NF-L (P < 0.001) and GFAp (P < 0.001) were higher in patients than in controls (TAU not analyzed in controls). The patient with most severe clinical and neuroradiological CNS-LCH displayed the highest levels of NF-L and GFAp whereas three patients without signs of systemic disease had low TAU levels and normal/slightly elevated NF-L. NF-L tended to be higher at radiological progression of neurodegeneration than at status quo (P = 0.07). Notably, we experienced frequent lumbar puncture complications in these patients. CONCLUSIONS: CSF levels of NF-L, TAU, and GFAp appear to be elevated in CNS-LCH. It would be valuable if these markers were validated in order to serve as markers for early CNS-LCH, to monitor disease progression and to evaluate various treatment attempts for CNS-LCH.


Assuntos
Proteínas do Líquido Cefalorraquidiano/análise , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Histiocitose de Células de Langerhans/líquido cefalorraquidiano , Degeneração Neural , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Adolescente , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Pré-Escolar , Transtornos Cognitivos/líquido cefalorraquidiano , Transtornos Cognitivos/etiologia , Progressão da Doença , Feminino , Seguimentos , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/patologia , Humanos , Lactente , Masculino , Doenças da Hipófise/líquido cefalorraquidiano , Doenças da Hipófise/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Radiografia , Punção Espinal/efeitos adversos , Adulto Jovem
10.
Pediatr Blood Cancer ; 51(5): 669-74, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18623210

RESUMO

BACKGROUND: Patients with Langerhans cell histiocytosis (LCH) may develop neurodegeneration and significant CNS sequelae, affecting a significant proportion of the patients. We here aimed to investigate the neuropsychological consequences in more detail. METHODS: Using an extensive neuropsychological test battery, we evaluated nine LCH patients, 6-20 years old, with radiological signs indicative of neurodegeneration. RESULTS: Altogether 3/9 patients performed below 1 SD of normal for age on full IQ. Detailed analysis revealed that 4/9 had deficient performance IQ, whereas 1/9 had subnormal verbal IQ (defined as below 1 SD). Furthermore, 3/8 patients showed slow speed of performance for age. Notably, 8/9 (89%) had deficient verbal working memory and 7/8 (88%) performed below normal on visual-spatial working memory. CONCLUSIONS: The results indicate a specific, uneven neuropsychological profile in patients affected by CNS-LCH, with a decline particularly on perceptual tasks whereas the verbal performance was not as negatively influenced. Furthermore, verbal and visual-spatial working memory functions were below normal for age in all but one patient studied. LCH may easily be misdiagnosed, but it is important that individuals affected by CNS-LCH are diagnosed to provide advice and support. It remains a challenge to find a treatment reducing this unfortunate neurodegeneration.


Assuntos
Encefalopatias/etiologia , Encefalopatias/patologia , Encéfalo/patologia , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/patologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/patologia , Feminino , Histiocitose de Células de Langerhans/psicologia , Humanos , Lactente , Masculino , Degeneração Neural/etiologia , Degeneração Neural/patologia , Testes Neuropsicológicos
11.
Pediatr Blood Cancer ; 51(1): 76-81, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18266220

RESUMO

BACKGROUND: Langerhans cell histiocytosis is a rare disease of unknown etiology. We wanted to assess the population-based incidence of LCH in a well-defined cohort of children. METHODS: We identified all children <15-years old treated with LCH during the 10 years period 1992-2001 at the Department of Pediatrics, Karolinska University Hospital in Stockholm, the referral center for children with LCH in Stockholm County. We also contacted the Departments of Dermatology, Orthopedics, and Neurosurgery for possible additional patients. RESULTS: Twenty-nine children (16 males) with LCH were identified, with a median age at diagnosis of 3.8 years (2 months-13.7 years). All children but one had a definitive diagnosis of LCH. The minimum incidence of LCH is estimated to 8.9/10(6) children per year. At diagnosis, 20 children (69%) had single system (SS) and 9 (31%) multisystem (MS) manifestations. Five of the 20 children with SS eventually developed MS disease, thus 14 (48%) had MS involvement at the maximal extent of disease (4.3/10(6) children per year). Interestingly, 22 children (76%) were diagnosed during the fall (September-November, n = 12) and winter (December-February, n = 10) seasons, as compared to seven children during the spring (March-May = 1) and summer (June-August = 6) seasons (P = 0.005, Chi-square). CONCLUSIONS: The incidence of childhood LCH in our study is higher than previously reported. In our patient cohort, LCH was more commonly diagnosed during the fall and winter season as compared to the spring and summer season. Whether this seasonal variation can be confirmed in larger studies and whether it has relevance for LCH pathophysiology remains to be elucidated.


Assuntos
Histiocitose de Células de Langerhans/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Medidas em Epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Estações do Ano , Suécia/epidemiologia
12.
Childs Nerv Syst ; 22(11): 1497-501, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16951966

RESUMO

CASE REPORT: We describe a 12-year-old boy with subarachnoid hemorrhage. Cerebral angiography revealed multiple fusiform intracranial arterial aneurysms. Surgical therapy other than ventricular drainage was not feasible due to the extent and pattern of pathological changes. Aspergillus antigen was found in the cerebrospinal fluid (CSF). However, cultures of urine, CSF, and samples from the upper airways were negative for Aspergillus and other fungi. The boy was immunocompromised due to prophylactic antibiotic therapy for recurrent pneumonia and continuous steroid therapy for his hemolytic anemia. There were Aspergillus antigens but no evidence of ongoing infection with the fungus was found. The patient suffered recurrent intraventricular hemorrhage and died on the 31st day after admission. PATHOLOGICAL EXAMINATION: Pathological examination showed multiple fusiform aneurysms, hypertrophy of the intima, and destruction of the internal elastic membrane of the cerebral arteries. No fungus infiltration was detected. We speculate that the patient had previously had an Aspergillus infection, causing segmental destruction of the internal elastic membrane. However, we cannot rule out noninfectious vasculitis as possible etiology. CONCLUSIONS: In the immunocompromised child, fusiform segmental intracranial arterial aneurysms may be secondary to the destruction of the internal elastic membrane by fungus infection. The condition may present with aneurysm rupture and subarachnoid hemorrhage. In this patient group, surgical therapy is rarely an option and the prognosis is poor.


Assuntos
Aneurisma Infectado , Aspergilose , Aspergillus/imunologia , Aneurisma Intracraniano , Anticorpos/líquido cefalorraquidiano , Aspergilose/complicações , Aspergilose/imunologia , Aspergilose/patologia , Angiografia Cerebral , Criança , Humanos , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/imunologia , Aneurisma Intracraniano/patologia , Masculino
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