Functional recovery of patients with intracerebral haemorrhage and cerebral infarction after rehabilitation.

To investigate potential differences in functional recovery after rehabilitation between intracerebral haemorrhage and cerebral infarction, we retrospectively compared the outcomes of patients with intracerebral haemorrhage (N = 208) and cerebral infarction (N = 480) who were consecutively discharged from our convalescent rehabilitation hospital between January 2013 and December 2018. Functional improvement was estimated by functional independence effectiveness measurements (proportion of potential for improvement achieved) upon discharge. Univariate analysis showed no significant differences in functional improvement between the two groups possibly because of the demographic variations upon admission. Multiple regression analysis demonstrated that the impact and type of factors related to functional improvement (functional independence measure upon admission, age, length of hospital stay, and time to admission after onset) were similar in both groups. Nevertheless, stratified analysis revealed, compared with patients with cerebral infarction, better improvement in patients with intracerebral haemorrhage that were admitted early after onset (<20 days), which exhibited high or moderate severity upon admission (functional independence measure: 36-89), or had a long hospital stay (>129 days). The present study showed differences as well as similarities in functional recovery between two stroke subtypes and suggests that better functional improvement might be expected in patients with intracerebral haemorrhage compared with those with cerebral infarction through an earlier start of intensive rehabilitation or longer rehabilitation in the hospital even if they exhibited relatively severe impairment upon admission. The type of stroke should be taken into consideration when predicting functional recovery and planning rehabilitation management in stroke patients.

Functional recoveries of patients with branch atheromatous disease after rehabilitation: Comparison with other types of cerebral infarction and importance of stratification by clinical categories.

BACKGROUND: Functional recoveries after rehabilitation of patients with branch atheromatous disease (BAD) have not been well investigated, however, clinical category of cerebral infarction including BAD itself could be a potential predictive factor for functional outcome. OBJECTIVE: To describe characteristics of functional recoveries of patients with BAD through comparison with other types of cerebral infarction. METHODS: We retrospectively compared outcomes of patients with BAD (N = 222), cardioembolic cerebral infarction (CE: N = 177) and atherothrombotic cerebral infarction (AT: N = 219) by using functional independence measure (FIM) and FIM effectiveness (the proportion of potential for improvement achieved). RESULTS: Univariate analysis showed that FIM on discharge was comparable among three types of cerebral infarction, but that FIM effectiveness in patients with BAD was significantly higher than those with CE or AT. Stratified analysis revealed higher FIM effectiveness in patients with BAD compared to patients with CE or AT, if they were male, younger (≤72 years) or had supratentorial brain lesions. Multiple regression analysis demonstrated that location of the brain lesion (supratentorial vs infratentorial) and gender (male vs female) were significantly associated with FIM on discharge, and that cognitive function on admission as well as gender were significantly associated with FIM effectiveness in patients with BAD, but not in patients with CE or AT. CONCLUSIONS: Outcomes after rehabilitation of patients with BAD may be characterized by better functional improvement, especially if patients are male, relatively younger or with supratentorial lesions. The impact and the type of factors related to functional recoveries of patients with BAD may be different from other types of stroke. The present study suggested that clinical category of stroke should be taken into consideration in prediction of outcomes and planning of rehabilitation management.

Effect of intensive rehabilitation on improvement of activity of daily living after intracerebral hemorrhage: a retrospective observational study.

Between 2008 and 2012, the intensity of rehabilitation therapy for the recovery phase of stroke was gradually increased at our hospital in line with the policy of Japan's National Insurance System. Training hours increased from 0.8 to 2.5 hours/day without introducing any new techniques, programs, or equipment. The aim of this study was to investigate the effectiveness of the increased intensity of rehabilitation on the improvement of activity of daily living of patients with intracerebral hemorrhage. We retrospectively compared patient outcomes for the periods 2013-2017 (N = 162) and 2003-2007 (N = 116) using the gain in Barthel Index as an indicator of improvement in activity of daily living. The median (interquartile range) gain was significantly higher in 2013-2017 than in 2003-2007 [30 (20-45) vs. 15 (5-30); P < 0.001]. A stratified analysis showed that this improvement was independent of sex, the patient's Barthel Index on admission, or the side of the brain lesion, but it varied with age or time to admission from onset of the disease. These results, based on a considerable difference in the intensity of rehabilitation between the two periods, support the consensus that increased time spent on rehabilitation results in better functional outcome in post-stroke patients. The results also suggest that age and the timing of starting rehabilitation are important factors to examine the effectiveness of intense rehabilitation in patients with intracerebral hemorrhage.

Apoptosis of T cells in peripheral blood and cerebrospinal fluid is associated with disease activity of multiple sclerosis.

Apoptotic elimination of pathogenic T cells is considered to be one of regulatory mechanisms in multiple sclerosis (MS). To explore the potential relationship between Fas-mediated apoptosis and the disease course of MS, we examined apoptosis, defined by annexin V (AV) binding, and Fas (CD95) expression in CD4+ and in CD8+ T cells in MS patients by using five-color flow cytometry. The percentage of AV+CD4+CD3+ cells and CD95+AV+CD4+CD3+ cells in peripheral blood and cerebrospinal fluid (CSF) were significantly decreased in active MS patients compared with inactive MS patients. A significantly lower proportion of CD95+AV+CD8+CD3+ cells in CSF was observed in active MS patients compared with inactive MS patients, but not in peripheral blood. These results indicate that the resistance of T cells to Fas-mediated apoptosis is involved in exacerbation of MS and/or that Fas-mediated apoptosis of T cells is associated with remission of MS.

The activation of memory CD4(+) T cells and CD8(+) T cells in patients with multiple sclerosis.

To reevaluate whether an association exists between the clinical course of multiple sclerosis (MS) and the activation of memory T cells, we investigated the phenotype of T cells in peripheral blood and cerebrospinal fluid (CSF) of patients with MS using five-color flow cytometry. A cross-sectional study with 39 relapsing-remitting MS patients demonstrated that the percentage of CD25(+)CD45RO(+)CD4(+)CD3(+) cells was significantly increased in peripheral blood as well as in CSF of active MS patients compared with inactive MS patients. A longitudinal study with 11 relapsing-remitting MS patients also showed a higher percentage of CD25(+)CD45RO(+)CD4(+)CD3(+) cells in peripheral blood at the phase of exacerbation than during remission. On the other hand, regardless of the disease activity, the percentage of CD25(+)CD45RO(+)CD8(+)CD3(+) cells in peripheral blood was significantly higher in patients with MS than in healthy control subjects. A lower percentage of CD25(+)CD45RO(+)CD8(+)CD3(+) cells in CSF was observed in active MS patients compared with inactive MS patients. These results suggest that the activation of memory CD4(+) T cells is associated with the exacerbation of MS and activation of memory CD8(+) T cells reflects systemic immunological dysregulation in MS patients. Transient as well as continuous activation of T cells by recall antigens may be involved in the disease course of MS.

[The role of apoptosis in autoimmune encephalomyelitis].

Experimental autoimmune encephalomyelitis(EAE), an inflammatory demyelinating disease of the central nervous system(CNS) provoked by myelin antigens, is widely used as a model for multiple sclerosis. Recent studies have shown that apoptosis may contribute to the death of oligodendrocytes and/or neurons, a pathological event leading to neurological deficits. On the other hand, the apoptotic elimination of inflammatory cells such as T cells and macrophages from the CNS is generally believed to contribute to the spontaneous recovery of EAE. Thus, apoptosis is involved in the disease-regulating as well as the disease-promoting processes of EAE.

Regulatory role of p53 in experimental autoimmune encephalomyelitis.

The role of p53, a pro-apoptotic protein, in experimental autoimmune encephalomyelitis (EAE) was investigated using p53-deficient C57BL/6J mice. p53-deficient mice immunised with myelin oligodendrocyte glycoprotein (MOG) exhibited a more severe clinical course of EAE with more severe inflammation in the central nervous system (CNS) compared to wild-type littermates. While T and B cell responses of p53-deficient mice to MOG were comparable to those of wild-type littermates, significantly higher production of IL-6, granulocyte macrophage colony-stimulating factor and IL-10 was observed in lymphocytes exposed to MOG from p53-deficient mice than those from wild-type littermates. Furthermore, a flow cytometric analysis of Annexin V staining showed that apoptosis of CNS-infiltrating cells was less in p53-deficient mice with EAE compared to wild-type littermates. These results suggest that p53 may be involved in the regulatory process of EAE through the control of cytokine production and/or the apoptotic elimination of inflammatory cells.

The suppression of T cell apoptosis influences the severity of disease during the chronic phase but not the recovery from the acute phase of experimental autoimmune encephalomyelitis in mice.

The elimination of T cells by apoptosis is considered to be one of the regulatory factors in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To address further the role of apoptotic T cell death in EAE, we investigated myelin oligodendrocyte glycoprotein (MOG)-induced EAE in transgenic mice overexpressing the anti-apoptotic gene, bcl-2, in T cells. During the acute phase of EAE, no significant difference was observed in the clinical course, pathology and T cell response to MOG between bcl-2 transgenic mice and wild-type littermates. While the recovery from the first attack of EAE was not impaired in the bcl-2 transgenic mice, a more severe disease was observed during the chronic phase of the disease even though T and B cell responses to MOG were comparable to those of wild-type littermates. A flow cytometric analysis by Annexin V showed a significant decrease of apoptotic T cells in the central nervous system (CNS) of the bcl-2 transgenic mice with EAE compared with controls during the chronic as well as the acute phase of disease. These results suggest that while T cell apoptosis in the CNS may play a regulatory role in EAE, the spontaneous recovery from acute EAE cannot solely be explained by T cell apoptosis.

Gender does not influence the susceptibility of C57BL/6 mice to develop chronic experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein.

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), is more prevalent in females than males. It is well documented that a significant gender difference exits in the susceptibility of mice to develop experimental autoimmune encephalomyelitis (EAE), a model of MS, induced by myelin basic protein or proteolipid protein. In contrast, we report here that no significant difference between female mice and male mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE was observed in the incidence of disease, clinical course, histological findings in the CNS, T cell response and cytokine production of spleen cells to MOG, and anti-MOG IgG level in serum. These results suggest that gender-related difference in EAE depends on the encephalitogen and/or the strain of animals used. Given that MOG is a putative pathogenic myelin antigen in MS, the present findings may have implications for the pathogenesis of this disease.