RESUMO
Autonomic cardiovascular reflexes were investigated in patients with an epidemic optic and peripheral neuropathy, which affected more than 50 000 people in Cuba between 1991 and 1994 and was probably caused by nutritional deficiency. Affected patients had significantly higher blood pressure than age matched controls, both while supine and standing, and significantly lower heart rate variability during paced breathing, suggesting reduced cardiac parasympathetic innervation.
Assuntos
Frequência Cardíaca , Hipertensão/fisiopatologia , Doenças do Nervo Óptico/fisiopatologia , Sistema Nervoso Parassimpático/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Adulto , Estudos de Casos e Controles , Cuba/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças do Nervo Óptico/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologiaRESUMO
In 1992-1994, a disorder known as the epidemic neuropathy afflicted more than 50,000 Cubans. Three different forms of the illness were identified: epidemic optic neuropathy, peripheral neuropathy and mixed optic and peripheral neuropathy. The causes are still unknown. Skeletal muscle biopsy samples were analyzed by standard histological techniques and by biochemical assays. Elevated activities of citrate synthase, a non-respiratory-chain mitochondrial matrix enzyme, suggested possible mitochondrial proliferation in 7 of the 8 patients. Nicotinamide adenine dinucleotide phosphate (NADP(+)) levels were higher in the patients than in the controls (p = 0.04). Levels of nicotinamide adenine dinucleotide (NAD) and the reduced compounds NADH and NADPH were comparable in patients and controls. Elevations of succinate dehydrogenase and citrate synthase activities and high NADP(+) levels suggest that alterations of mitochondrial functions may be associated with this disorder.
Assuntos
Doenças Mitocondriais/enzimologia , Doenças do Nervo Óptico/enzimologia , Oxirredutases/metabolismo , Doenças do Sistema Nervoso Periférico/enzimologia , Adulto , Citrato (si)-Sintase/metabolismo , Cuba/epidemiologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Pessoa de Meia-Idade , Doenças Mitocondriais/epidemiologia , Músculo Esquelético/enzimologia , NADP/metabolismo , Doenças do Nervo Óptico/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Succinato Citocromo c Oxirredutase/metabolismo , Succinato Desidrogenase/metabolismoRESUMO
Twenty-one amino acids were determined in serum and cerebrospinal fluid of 12 patients with endemic, and in the cerebrospinal fluid of 22 patients with epidemic optic neuropathy. For the endemic patients, there was a decrease in aspartate and taurine in the serum with respect to controls. The ratios aspartate/taurine and taurine/valine were decreased, and glutamate/taurine was increased in the serum. Some of the altered amino acid ratios indicate preponderance of excitatory to inhibitory molecules. The ratio with valine corresponded to the decrease in taurine and the maintenance of valine concentration, an amino acid related to anthropometric parameters. A typical malnutrition pattern was not observed, as the levels of essential amino acids were not significantly modified. In the cerebrospinal fluid there were increases in aspartate, glutamate and threonine, the first two probably indicating a neurodegenerative disorder or some type of metabolic alteration, primary or secondary to the disease. The increase in threonine could be related to lipid metabolism, but it is not clear at present. A wide variety of amino acid ratios were increased in the cerebrospinal fluid of patients with endemic optic neuropathy, mainly pointing to an excitatory condition and some metabolic alterations. In the cerebrospinal fluid of patients with epidemic optic neuropathy there was an increase in aspartate and glutamate, and increase in glutamate/taurine, glutamate/glycine, and gamma-aminobutyric acid/glycine ratios. Interesting differences were also observed between patients from different periods of time, but with the same clinical features, and the modifications of amino acid concentrations in the cerebrospinal fluid, such as glutamine, threonine and tryptophan. The present results indicate a disorder in the metabolism of amino acids, support a specific deficit, especially for taurine, an imbalance between excitatory and inhibitory amino acids, and a possible relation to viral infections.
Assuntos
Aminoácidos/sangue , Doenças do Nervo Óptico/sangue , Adulto , Aminoácidos/líquido cefalorraquidiano , Antropometria , Cuba/epidemiologia , Surtos de Doenças , Doenças Endêmicas/estatística & dados numéricos , Humanos , Doenças do Nervo Óptico/líquido cefalorraquidiano , Doenças do Nervo Óptico/epidemiologia , Valores de ReferênciaRESUMO
INTRODUCTION: The mitochondria, subcellular organelles which possess their own DNA (mtDNA), produce most of the energy, in the form of ATP, which is necessary for life. This mtDNA may have diverse molecular defects which have been associated with a great variety of clinical syndromes. Deletions in mtDNA are one of the common mutations in patients with mitochondrial myopathies, which in the great majority present with the common symptom of progressive external ophthalmoplegia. In this study we report our findings in eight Cuban families with suspected mitochondrial disease. OBJECTIVES: To characterize these patients from the molecular point of view, which would allow a preliminary understanding of the behavior of these deletions in Cuban patients. PATIENTS AND METHODS: We studied nine patients from eight Cuban families in whom mitochondrial encephalomyopathy was suspected. We analyzed the presence of ragged red fibres, the enzymatic activity of the mitochondrial respiratory chain and detection of mtDNA mutations. We used the technique of restriction length polymorphism analysis for detection of deletions. RESULTS: Histochemical studies showed the presence of COX negative ragged red fibres in seven of the patients studied. The enzymatic activity of the mitochondrial respiratory chain was normal in all the patients. We detected four patients with single deletions of mtDNA, and one with multiple deletions and of the patients had the A3243G mutation. CONCLUSIONS: With the methods used we were able to determine the presence of a mitochondrial disorder in seven of the eight families studied and deletions of mtDNA were detected as the cause of the illness in five. The disorder was always associated with progressive external ophthalmoplegia and COX negative ragged red fibres.
Assuntos
DNA Mitocondrial/genética , Oftalmoplegia Externa Progressiva Crônica/epidemiologia , Oftalmoplegia Externa Progressiva Crônica/genética , Adolescente , Adulto , Southern Blotting , Cuba/epidemiologia , Análise Mutacional de DNA , Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Deleção de Genes , Humanos , Imuno-Histoquímica , Masculino , Oftalmoplegia Externa Progressiva Crônica/enzimologia , Mutação Puntual/genética , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: The 2D VEPs to pattern reversal (PR) and LED goggle were studied in order to obtain a stable parameter for the functional assessing of posterior visual pathways regardless of the stimulus type used. DESIGN AND METHODS: Apex c latency, bc segment amplitude (V), and bc vector orientation angle (theta) in voltage space were computed from VEPs recorded in 50 normal human beings and two patients with left posterior brain lesions, in an orthogonal Fpz-Oz and T3-T4 montage and displayed as a two channel Lissajous' trajectory. The effects of stimulus type and stimulated eye were analyzed in the normal group by a two-way ANOVA. RESULTS: The stimulated eye had no effect on any parameter. Apex c latency was slightly longer, and V was greater and more variable in the responses to goggle stimuli, but there was no significant difference in theta, oriented to mid-occipital scalp with very low variability for both stimulus types. The patients showed significant deviations of theta towards the affected hemisphere. CONCLUSIONS: The bc vector orientation (theta) is a stable parameter for the evaluation of the posterior visual pathways using both pattern reversal and LED stimuli, specially the latter, useful in unconscious or uncooperative patients.
Assuntos
Potenciais Evocados Visuais/fisiologia , Reconhecimento Automatizado de Padrão , Adolescente , Adulto , Encéfalo/fisiologia , Mapeamento Encefálico , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação LuminosaRESUMO
Nearly 51,000 Cubans were afflicted during an outbreak of an optic neuropathy (ON) and peripheral neuropathy (PN) between 1991 and 1993. We re-examined 14 of 20 affected individuals 16 months after an initial evaluation. The optic features were painless symmetric vision loss with poor visual acuity, color vision loss, central or cecocentral scotoma, optic disc pallor, and nerve fiber layer drop-out. The neurologic symptoms included stocking-glove sensory changes, hearing loss, leg cramps, sensory ataxia, hyperactive or absent reflexes, and complaints of memory loss. Two of 11 ON probands tested harbored Leber's hereditary optic neuropathy (LHON)-associated mitochondrial DNA mutations. All patients had received multivitamin therapy. We performed comparisons using the paired two-tailed t test. On re-examination, 12 of 14 patients demonstrated improvement. One patient remained unchanged. One woman with the nt-3460 mtDNA mutation showed a decline in vision. In patients not harboring mtDNA mutations, overall visual acuity, color vision, and peripheral neuropathy manifestations improved significantly (p < 0.001 for each manifestation). Most of the patients with Cuban ON and PN improved on multivitamin therapy. The significance of the mtDNA mutations is unclear. In the 2 LHON patients, manifestation of the disease may have been precipitated by nutritional deficiency. Patients with poor recovery or further deterioration should be evaluated for other factors, including poor vitamin therapy compliance and alternative diagnoses.
Assuntos
Surtos de Doenças , Doenças do Nervo Óptico/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Adulto , Estudos de Coortes , Percepção de Cores/efeitos dos fármacos , Cuba , DNA Mitocondrial/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Exame Neurológico , Atrofias Ópticas Hereditárias/tratamento farmacológico , Atrofias Ópticas Hereditárias/genética , Atrofias Ópticas Hereditárias/fisiopatologia , Doenças do Nervo Óptico/complicações , Doenças do Nervo Óptico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/complicações , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Resultado do Tratamento , Acuidade Visual/efeitos dos fármacos , Vitaminas/uso terapêuticoRESUMO
Since October 1991, nearly 51,000 Cubans have been afflicted in an outbreak of optic and peripheral neuropathies. To begin an investigation of the possible role of mitochondrial DNA (mtDNA) mutations in the outbreak, we studied mtDNA from 14 affected and two unaffected Cubans for the 12 mutations associated with Leber's hereditary optic neuropathy. Eleven probands (12 patients) had optic neuropathy and two had peripheral neuropathy only. We also studied two unaffected relatives of one proband. We identified two mtDNA mutations, at nucleotides 11778 and 3460, in two of the 11 probands with optic neuropathy. Although this data set is too small to reach statistically valid conclusions, it does suggest that mtDNA mutations might be contributing to the outbreak of optic neuropathy in Cuba.
Assuntos
DNA Mitocondrial , Mutação , Atrofias Ópticas Hereditárias/genética , Sequência de Bases , Cuba/epidemiologia , Surtos de Doenças , Humanos , Dados de Sequência Molecular , Atrofias Ópticas Hereditárias/epidemiologiaRESUMO
Visual evoked potentials and electroretinograms were elicited by light-emitting diode stimulation and recorded simultaneously, with cephalic and noncephalic references, in 30 normal subjects and in 30 brain-dead patients. A characteristic pattern was found in the group of patients: when a cephalic reference was used for both visual evoked potentials and the electroretinogram, the a- and b-waves of the electroretinogram were recognized in all patients, and visual evoked responses consisted of waves with inverse polarity, similar morphologic characteristics, the same latency, and less amplitude than those of the electroretinogram. When a noncephalic derivation was chosen for the electroretinogram and visual evoked potentials, electroretinogram did not change in either morphologic features or latency, whereas the visual evoked potential channel showed no response. Only in two cases was it possible to record waves in the visual evoked potential lead with a noncephalic reference, showing a spread of the electroretinogram to the occipital area, with a considerably reduced amplitude. These results suggest that, although contamination of visual evoked potential records by the spread of the electroretinogram to the occipital area could occur, it is easy to confirm the absence of a true cortical visual response in brain-dead patients by means of a noncephalic reference. This pattern clearly confirms that in the visual pathways of brain-dead patients, electrical activity is confined to the retina.