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OBJECTIVE: To analyze the effect of mecobalamin on the early-functional outcomes of patients with ischemic stroke and H-type hypertension. METHODS: From October of 2014 to October of 2016, 224 cases of ischemic stroke and H-type hypertension were selected. The patients were randomly divided into treatment control groups, with 112 patients in each group. The control group was treated with the conventional therapy. The observation group was treated with 500 µg of mecobalamin three times a day in addition to the conventional therapy. We compared serum homocysteine (Hcy), hs-CRP levels, carotid plaques, and NIHSS scores between the two groups on the 2nd day and at 4 weeks, 8 weeks, 3 months, and 6 months. RESULTS: After 4 weeks, 8 weeks, 3 months and 6 months, the difference of serum Hcy level between the two groups was statistically significant (t = 4.049, 3.896, 6.052, 6.159, respectively. All P <0.05). After the treatment, at 4 weeks, 8 weeks, 3 months and 6 months, the levels of hs-CRP in the treatment group were significantly lower than those in the control group (t = 37.249, 28.376, 26.454, 20.522, respectively. All P <0.01). After 3 months and 6 months, the carotid artery plaques were significantly reduced in the treatment group compared to those in the control group (t = 2.309 and 2.434. All P <0.05). After 3 months and 6 months, the NIHSS score was significantly higher in the treatment group compared to those in the control group (t = 2.455 and 2.193. All P <0.05). CONCLUSION: Mecobalamin can reduce the level of plasma homocysteine, then lead to reductions of levels of plasma inflammatory factors and volume of carotid artery plaques, resulting in more significant functional recovery.

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SUMMARY OBJECTIVE To analyze the effect of mecobalamin on the early-functional outcomes of patients with ischemic stroke and H-type hypertension. METHODS From October of 2014 to October of 2016, 224 cases of ischemic stroke and H-type hypertension were selected. The patients were randomly divided into treatment control groups, with 112 patients in each group. The control group was treated with the conventional therapy. The observation group was treated with 500 µg of mecobalamin three times a day in addition to the conventional therapy. We compared serum homocysteine (Hcy), hs-CRP levels, carotid plaques, and NIHSS scores between the two groups on the 2nd day and at 4 weeks, 8 weeks, 3 months, and 6 months. RESULTS After 4 weeks, 8 weeks, 3 months and 6 months, the difference of serum Hcy level between the two groups was statistically significant (t = 4.049, 3.896, 6.052, 6.159, respectively. All P <0.05). After the treatment, at 4 weeks, 8 weeks, 3 months and 6 months, the levels of hs-CRP in the treatment group were significantly lower than those in the control group (t = 37.249, 28.376, 26.454, 20.522, respectively. All P <0.01). After 3 months and 6 months, the carotid artery plaques were significantly reduced in the treatment group compared to those in the control group (t = 2.309 and 2.434. All P <0.05). After 3 months and 6 months, the NIHSS score was significantly higher in the treatment group compared to those in the control group (t = 2.455 and 2.193. All P <0.05). CONCLUSION Mecobalamin can reduce the level of plasma homocysteine, then lead to reductions of levels of plasma inflammatory factors and volume of carotid artery plaques, resulting in more significant functional recovery.

RESUMO OBJETIVO Analisar o efeito de mecobalamin sobre os primeiros resultados funcionais de pacientes com AVC isquêmico e hipertensão H-type. MÉTODOS De outubro de 2014 a outubro de 2016, 224 casos de AVC isquêmico e hipertensão H-type foram selecionadas. Os pacientes foram divididos aleatoriamente em grupo de tratamento e grupo controle, com 112 doentes em cada grupo. O grupo controle foi tratado com a terapia de rotina. O grupo de observação foi tratado com 500 µg de mecobalamin três vezes por dia, além da rotina de tratamento. No segundo dia, 4 semanas, 8 semanas, 3 meses e 6 meses, comparamos níveis séricos da homocisteína (Hcy) e de hs-CRP, placas da carótida e pontuações NIHSS entre os dois grupos. RESULTADOS Após 4 semanas, 8 semanas, 3 meses e 6 meses, a diferença dos níveis séricos de Hcy entre os dois grupos foi estatisticamente significativa (t= 4,049, 3,896, 6,052, 6,159, respectivamente. Todos os P<0,05). Após o tratamento de 4 semanas, 8 semanas, 3 meses e 6 meses, os níveis de hs-CRP no grupo de tratamento foram significativamente inferiores aos do grupo controle (t=37,249, 28,376, 26,454, 20,522, respectivamente. Todos os P<0,01). Depois de 3 meses e 6 meses, as placas da artéria carótida foram significativamente reduzidas no tratamento, em comparação com os do grupo controle (t=2,309 e 2,434. Todos os P<0,05). Depois de 3 meses e 6 meses, as pontuações NIHSS foram significativamente mais elevadas no tratamento em comparação com as do grupo controle (t=2,455 e 2,193. Todos os P<0,05). CONCLUSÃO Mecobalamin pode reduzir o nível de homocisteína plasmática, o que conduz à redução dos níveis de plasma inflamatórios e do volume das placas na artéria carótida, resultando em maior recuperação funcional.

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We report here the clinical, genetic and molecular characterization of four Han Chinese families with Leber's hereditary optic neuropathy (LHON). The penetrances of optic neuropathy in these Chinese pedigrees were 38%, 38%, 44% and 56%. This observation is in contrast with the previously identified 14 Chinese families with very low penetrance of LHON. The age-at-onset for visual impairment in matrilineal relatives in these Chinese families varied from 18 to 30years. Furthermore, the ratios between affected male and female matrilineal relatives in these families were 3:0, 3:0, 3:1 and 2:3, respectively. Molecular analysis of mitochondrial genomes identified the known ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M9a. Of these, the ND1 T3394C mutation caused the substitution of a highly conserved histidine for tyrosine (Y30H) at amino acid position 30. This mutation was associated with LHON in other families with low penetrance of optic neuropathy and other clinical abnormalities. The presence of both G11778A and T3394C mutations appears to contribute to higher penetrance of optic neuropathy in these four Chinese families than other Chinese families carrying only the G11778A mutation. Therefore, the mitochondrial haplogroup M9a specific variant T3394C may modulate the phenotypic manifestation of LHON-associated G11778A mutation in these Chinese pedigrees.

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We report here the clinical, genetic, and molecular evaluations of four Han Chinese families with Leber's hereditary optic neuropathy. Thirty-one (20 males/11 females) of 83 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual impairment. The average age-of-onset of vision loss was 22years old. Strikingly, these penetrances of visual impairment in these Chinese families were higher than those in other 11 Chinese pedigrees carrying the only ND4 G11778A mutation. Molecular analysis identified the known G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M10a and M7c2. Of these, the T14502C mutation caused the substitution of a highly conserved isoleucine for valine at position 58 in ND6. This mutation has been associated with LHON in other Chinese families with very low penetrance of LHON. Thus, the deficient activities of complex I, caused by G11778A mutation, would be worsened by the T14502C mutation in these four Chinese families. As a result, mitochondrial dysfunctions would lead to the high penetrance and expressivity of visual loss in these Chinese families carrying both G11778A and T14502C mutations than other 11 Chinese families carrying only G11778A mutation. These data suggested that the T14502C variant may modulate the phenotypic manifestation of the G11778A mutation in these Chinese pedigrees.

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BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder. The purpose of this investigation is to understand the role of mitochondrial haplotypes in the development of LHON associated with ND6 T14484C mutation in Chinese families. METHODS: One hundred fourteen subjects from ten Han Chinese families with LHON were studied by the clinical and genetic evaluation as well as molecular and biochemical analyses of mitochondrial DNA (mtDNA). RESULTS: Clinical evaluation revealed that ten families exhibited extremely low penetrance of visual impairment, with an average of 10%. In particular, ten (8 males/2 females) of 114 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The average age-of-onset of vision loss was 19 years old. Molecular analysis of mitochondrial DNA (mtDNA) identified the homoplasmic T14484C mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, D4, D4g1b, G3a2, R11, R11a and Z3, respectively. However, there was the absence of secondary LHON-associated mtDNA mutations in these ten Chinese families. CONCLUSION: The low penetrance of vision loss in these Chinese pedigrees strongly indicated that the T14484C mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the T14484C mutation in those Chinese families with low penentrace of vision loss. However, nuclear modifier genes and environmental factors appear to be modifier factors for the phenotypic manifestation of the T14484C mutation in these Chinese families.

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We report here the clinical, genetic, and molecular characterization of three Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age of onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T14502C (I58V) mutation, which localized at a highly conserved isoleucine at position 58 of ND6, and distinct sets of mtDNA polymorphisms belonging to haplogroups M10a, F1a1, and H2. The occurrence of T14502C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Here, mtDNA variants I187T in the ND1, A122V in CO1, S99A in the A6, and V254I in CO3 exhibited an evolutionary conservation, indicating a potential modifying role in the development of visual impairment associated with T14502C mutation in those families. Furthermore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic manifestation of the LHON-associated T14502C mutation in these Chinese families.

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We report here the clinical, genetic and molecular characterization of four Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age-of-onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T3394C (Y30H) mutation, which localized at a highly conserved tyrosine at position 30 of ND1, and distinct sets of mtDNA polymorphisms belonging to haplogroups D4b and M9a. The occurrence of T3394C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. However, there was the absence of functionally significant mtDNA mutations in these four Chinese pedigrees carrying the T3394C mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated T3394C mutation.

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