RESUMO
Glutaric acidemia type I (GA1) is caused by severe deficiency of glutaryl-CoA dehydrogenase activity, resulting in an accumulation of glutaric acid and glutarylcarnitine (C5DC) in the organism. Patients affected by GA1 are asymptomatic in the neonate period but usually manifest chronically progressive neurodegeneration apart from severe encephalopathic crises associated with acute striatum necrosis. Neurological manifestations like dyskinesia, dystonia, hypotonia, muscle stiffness, and spasticity are present. Treatment is based on protein/lysine restriction and l-carnitine supplementation. In this work, we evaluated markers of neurodegeneration and inflammation, namely BDNF (brain-derived neurotrophic factor), NCAM (neuronal adhesion molecule), PDGF-AA (platelet-derived growth factor), and cathepsin-d in plasma of six treated GA1 patients. We first found marked increases of plasma C5DC concentrations in GA1 patients, as well as increased levels of the markers BDNF and cathepsin-d as compared to those of age-matched healthy children. Furthermore, C5DC concentrations were highly correlated with the levels of cathepsin-d. These results may demonstrate that brain tissue degeneration is present in GA1 patients and that there is a relationship between increased metabolites concentrations with this process. To the best of our knowledge, this is so far the first study showing altered peripheral parameters of neurodegeneration and inflammation in GA1 patients.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/sangue , Encefalopatias Metabólicas/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Catepsina D/sangue , Glutaril-CoA Desidrogenase/deficiência , Degeneração Neural/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Biomarcadores/sangue , Encefalopatias Metabólicas/complicações , Criança , Pré-Escolar , Feminino , Glutaril-CoA Desidrogenase/sangue , Humanos , Lactente , Recém-Nascido , Masculino , Degeneração Neural/sangue , Degeneração Neural/etiologia , Moléculas de Adesão de Célula Nervosa/sangue , Fator de Crescimento Derivado de Plaquetas/metabolismoRESUMO
INTRODUCTION: Dopamine depletion is one of the most important features of Parkinson's Disease (PD). However, insufficient response to dopaminergic replacement therapy suggests the involvement of other neurotransmitter systems in the pathophysiology of PD. Cholinergic degeneration contributes to gait impairments, cognitive impairment, psychosis, and REM-sleep disturbances, among other symptoms. Areas covered: In this review, we explore the idea that enhancing cholinergic tone by pharmacological or neurosurgical procedures could be a first-line therapeutic strategy for the treatment of symptoms derived from cholinergic degeneration in PD. Expert opinion: Rivastigmine, a drug that increases cholinergic tone by inhibiting the enzyme cholinesterase, is effective for dementia, whereas the use of Donepezil is still in the realm of investigation. Interesting results suggest the efficacy of these drugs in the treatment of gait dysfunction. Evidence on the clinical effects of these drugs for psychosis and REM-sleep disturbances is still weak. Stimulation of the pedunculo-pontine tegmental nuclei (which provide cholinergic innervation to the brain stem and subcortical nuclei) has also been used with some success for the treatment of gait dysfunction. Anticholinergic drugs should be used with caution in PD, as they may aggravate cholinergic symptoms. Notwithstanding, in some patients they might help control parkinsonian motor symptoms.
Assuntos
Colinérgicos/uso terapêutico , Neurônios Colinérgicos/patologia , Degeneração Neural/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Animais , Colinérgicos/farmacologia , Neurônios Colinérgicos/efeitos dos fármacos , Ensaios Clínicos como Assunto/métodos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/epidemiologia , Demência/diagnóstico , Demência/dietoterapia , Demência/epidemiologia , Donepezila , Marcha/efeitos dos fármacos , Humanos , Indanos/farmacologia , Indanos/uso terapêutico , Degeneração Neural/diagnóstico , Degeneração Neural/epidemiologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologiaRESUMO
OBJECTIVES: It was the aim of this study to evaluate if the quantitative intrathecal immunoglobulin G (IgG) synthesis correlates with the brain atrophy and the total lesion volume (TLV) in brain magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients. METHODS: A total of 50 patients with relapsing-remitting MS were included in this study. MRIs were performed and cerebrospinal fluid samples were collected during the diagnostic determination when patients were in remission without treatment. RESULTS: At study baseline, IgG index values were elevated in 36 patients (72%), and oligoclonal IgG bands were positive in 42 of 50 patients (84%). Brain MRI was abnormal in 94% of patients, and, compared with healthy controls, brain atrophy was observed in MS patients. A positive correlation among IgG index, cerebrospinal fluid leukocyte count and TLV was observed; the Expanded Disability Status Scale correlated positively with TLV and the number of lesions, although a significant relationship between disability and brain atrophy was not demonstrated. CONCLUSIONS: Although new parameters will be necessary in longitudinal studies to characterize the axonal injury in various stages of the disease, the data suggest that the high intrathecal IgG synthesis may predict a greater brain lesion burden.
Assuntos
Dano Encefálico Crônico/líquido cefalorraquidiano , Dano Encefálico Crônico/diagnóstico , Encéfalo/patologia , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico , Bandas Oligoclonais/líquido cefalorraquidiano , Adolescente , Atrofia/líquido cefalorraquidiano , Atrofia/diagnóstico , Atrofia/imunologia , Encéfalo/imunologia , Encéfalo/fisiopatologia , Dano Encefálico Crônico/imunologia , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/metabolismo , Proteínas do Líquido Cefalorraquidiano/análise , Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/imunologia , Criança , Avaliação da Deficiência , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Degeneração Neural/líquido cefalorraquidiano , Degeneração Neural/diagnóstico , Degeneração Neural/imunologia , Bandas Oligoclonais/biossíntese , Valor Preditivo dos TestesRESUMO
BACKGROUND AND PURPOSE: Hyperintensity in the posterior limb of the internal capsule at T2-weighted MR imaging, consistent with corticospinal tract (CST) degeneration, is described in amyotrophic lateral sclerosis (ALS). However, the lack of specific tests or biological markers hinders confirmation of the diagnosis, especially in the early stages. We investigated the CST in ALS with MR imaging. METHODS: We examined 25 patients (14 men, 11 women; mean age, 49.1 years; range, 29-68 years) and 21 age- and sex-matched control subjects without upper motor neuron signs. According to the revised El Escorial criteria, 22 patients had definite ALS; two, probable ALS; and one, suspected ALS. Fluid-attenuated inversion recovery (FLAIR; TR/TE/TI, 11,000/140/2600) and T1-weighted spin-echo (SE)/magnetization transfer contrast-enhanced (MTC; TR/TE, 510/12) imaging was performed at 1 T. Two experienced neuroradiologists blinded to the patients' history independently evaluated the CST. RESULTS: T1-weighted SE MTC imaging allowed visualization of the CST in both patients and control subjects. T1-weighted SE MTC images showed hypointensity along the CST and bilateral subcortical regions of the precentral gyri in all control subjects and hyperintensity in 80% of patients with ALS (P < .05). FLAIR images showed hyperintensity in these areas in both groups, with no significant difference. CONCLUSION: T1-weighted SE MTC imaging is sensitive and accurate in depicting CST lesions in ALS, whereas FLAIR imaging is not. T1-weighted SE MTC imaging is useful in diagnosing ALS by showing hyperintense areas along the CST, which separates patients from control subjects. This sequence should be included in the workup of patients with weakness and pyramidal signs.
Assuntos
Aumento da Imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Doença dos Neurônios Motores/diagnóstico , Degeneração Neural/diagnóstico , Tratos Piramidais/patologia , Adulto , Idoso , Córtex Cerebral/patologia , Feminino , Humanos , Cápsula Interna/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Cellular and molecular mechanisms involved in the generation of seizures and the magnitude of neural cells injury are not fully understood. We evaluated astrocyte and/or neuronal injury in rats in the pentylenetetrazol model of acute seizures by measuring S100B and NSE levels in cerebrospinal fluid. Additionally, we determined ADP and GDP hydrolysis by soluble nucleoside triphosphate diphosphohydrolase in the cerebrospinal fluid, and the concentration of nucleosides adenosine, inosine and guanosine as putative markers of brain injury. After pentylenetetrazol-induced seizures: (i) S100B values increased from 10 to 30 min, returning to control levels at 24 h; NSE levels presented a biphasic increase: an increase at 10 to 30 min returning to control levels, and again at 240 min followed by a decline at 24 h; (ii) nucleotidase activities increased from 10 min, returning to control levels at 240 min; (iii) guanosine and inosine levels increased exclusively after 30 min. In summary, this study showed biochemical changes in the cerebrospinal fluid occurring after seizures induced by pentylenetetrazol. Such events may have a modulating effect upon seizure expression, particularly nucleoside triphosphate diphosphohydrolase activities and nucleoside concentrations, but are nevertheless followed by neural death as evidenced by the increase in NSE and S100B levels.
Assuntos
Encéfalo/metabolismo , Degeneração Neural/líquido cefalorraquidiano , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Purinas/líquido cefalorraquidiano , Convulsões/líquido cefalorraquidiano , Adenosina/líquido cefalorraquidiano , Difosfato de Adenosina/metabolismo , Animais , Antígenos CD/líquido cefalorraquidiano , Apirase/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Encéfalo/fisiopatologia , Convulsivantes , Modelos Animais de Doenças , Feminino , Guanosina/farmacologia , Guanosina Difosfato/metabolismo , Hidrólise , Inosina/farmacologia , Degeneração Neural/diagnóstico , Degeneração Neural/fisiopatologia , Fatores de Crescimento Neural/líquido cefalorraquidiano , Pentilenotetrazol , Fosfopiruvato Hidratase/líquido cefalorraquidiano , Ratos , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/líquido cefalorraquidiano , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration involving the dento-rubro-olivary pathway and presents clinically as palatal tremor. We present a 48 year old male patient who developed Holmes' tremor and bilateral HOD five months after brainstem hemorrhage. The severe rest tremor was refractory to pharmacotherapy and botulinum toxin injections, but was markedly reduced after thalamotomy. Magnetic resonance imaging permitted visualization of HOD, which appeared as a characteristic high signal intensity in the inferior olivary nuclei on T2- and proton-density-weighted images. Enlargement of the inferior olivary nuclei was also noted. Palatal tremor was absent in that moment and appears about two months later. The delayed-onset between insult and tremor following structural lesions of the brain suggest that compensatory or secondary changes in nervous system function must contribute to tremor genesis. The literature and imaging findings of this uncommon condition are reviewed.
Assuntos
Hemorragia Cerebral/complicações , Degeneração Neural/etiologia , Núcleo Olivar/patologia , Tremor/etiologia , Humanos , Hipertrofia/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Degeneração Neural/diagnóstico , Tomografia Computadorizada por Raios X , Tremor/diagnóstico , Tremor/patologiaRESUMO
A demência com corpos de Lewy (DCL) vem recebendo atençäo crescente nos últimos anos e de acordo com muitos autores é considerada a segunda causa de demência degenerativa no idoso. A DCL é uma entidade que atualmente preenche critérios clínicos e neuropatológicos propostos por consenso internacional, geralmente aceito, e que permitem considerar esse diagnóstico na prática clínica desde o início do atendimento de um paciente demenciado. O diagnóstico desse quadro complexo se baseia na presença de comprometimento cognitivo (onde se destacam flutuaçöes de desempenho) que evolui para demência, manifestaçöes näo-cognitivas (com presença de alucinaçöes visuais precocemente) e sinais parkinsonianos espontâneos muito freqüentes. Tais manifestaçöes apresentam características muito sugestivas de DCL possível/provável . A presente revisäo visa analisar a evoluçäo do conceito, os aspectos neuropatológicos e clínicos, além das dificuldades diagnósticas da DCL
Assuntos
Humanos , Masculino , Feminino , Transtornos Cognitivos/etiologia , Degeneração Neural/diagnóstico , Demência/etiologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnósticoRESUMO
Säo demonstradas alteraçöes transitórias bipalidais caracterizadas por hiperintensidade na sequência T1 da ressonância nuclear magnética, que ocorreram em um paciente com degeneraçäo hepatocerebral adquirida provocada por hemocromatose. Em funçäo de acrescentar-se a este sinal a visibilizaçäo de imagem de hiperintensidade bitalâmica na sequência T2, discute-se a hipótese destes sinais serem unicamente secundários â degeneraçäo hepatocerebral ou, ainda, se teriam sido também originados pela própria hemocromatose.
Assuntos
Pessoa de Meia-Idade , Humanos , Masculino , Hemocromatose/complicações , Encefalopatia Hepática/etiologia , Degeneração Neural/etiologia , Encefalopatia Hepática/diagnóstico , Espectroscopia de Ressonância Magnética , Degeneração Neural/diagnósticoRESUMO
Transitory changes are shown through T1-weighted MRI bipallidal hyperintensity in a patient with acquired hepatocerebral degeneration induced by hemochromatosis. In addition we discuss about the possibility of this image associated with thalamic hyperintensity on T2-weighted also seen in this case, was just secondary to hepatocerebral degeneration, or if they could be caused by hemochromatosis itself.