The effects of neuromuscular facilitation techniques on osteoporosis of hemiplegia limbs and serum leptin level in patients or rats with cerebral infarction.

PRIMARY OBJECTIVE: This study was to investigate the effect of proprioceptive neuromuscular facilitation techniques (NFT) on osteoporosis and serum leptin level in cerebral infarction patients or rats. RESEARCH DESIGN: Forty cerebral infarction rats were randomly grouped into control, sham operation, conventional treatment (CT) group and CT+NFT group. Fifty-two stroke patients with hemiplegia were included in this study. METHODS AND PROCEDURES: The bone mineral densities (BMD) of proximal hemiplegia limbs and serum ALP, BALP, BGP, IL-6 and leptin levels were detected using commercial kits. MAIN OUTCOMES AND RESULTS: In cerebral infarction rats, the BMD, BGP, BALP, ALP and leptin concentrations in the CT+NFT group was higher compared with the control and CT group, while serum IL-6 level was more reduced by CT+NFT than control and CT. In cerebral infarction patients, both CT and CT+NFT increased the BMD, ALP, BGP and leptin levels. In addition, compared with CT, the BMD, ALP, BGP and leptin levels were markedly increased by CT+NFT. C Conclusion: NFC elevated the BMD of hemiplegia limbs, serum ALP, BGP, IL-6 and leptin levels and, thus, alleviated osteoporosis in rats and patients with cerebral infarction.

Vitamin D profile of patients with spinal cord injury and post-stroke hemiplegia: All in the same boat.

BACKGROUND: Patients with spinal cord injury (SCI) and hemiplegia are at risk of fractures partly due to decreased bone mineral density with relation to the low levels of vitamin D. OBJECTIVE: The objective of this study is to evaluate the vitamin D profile of patients with SCI and post-stroke hemiplegia. METHODS: 25(OH)D levels of patients with SCI and hemiplegia were obtained from the electronic medical record database and compared with age- and sex-matched non-disabled controls. Furthermore, the effect of Functional Ambulation Category (FAC), American Spinal Injury Association (ASIA) level and Brunnstrom's recovery stage, on vitamin D insufficiency, was studied. RESULTS: The study sample consisted of 173 individuals (118 patients and 55 controls). Vitamin D levels and sufficiency rates of the neurologically disabled patients was significantly lower than that of controls (p= 0.000 and p= 0.000, respectively). However, there was no difference between patients with SCI and hemiplegia regarding the 25(OH)D levels and vitamin D insufficiency (p= 0.303 and p= 0.952, respectively). There were no statistically significant differences in vitamin D status by American Spinal Injury Association (ASIA) level and Brunnstrom's score. However, regression analysis revealed that vitamin D insufficiency rate of non-functionally ambulatory (FAC = 0-2) patients was higher than that of functionally ambulatory (FAC = 3-5) ones (p= 0.044). CONCLUSIONS: Vitamin D status of patients with neurological disabilities was lower than that of controls. Non-functionally ambulatory patients had higher vitamin D insufficiency rate than functionally ambulatory patients. Preventative measures including adequate supplementation of vitamin D should be directed to neurologically disabled subjects, particularly those with non-functional ambulation.

Electroacupuncture reduces hemiplegia following acute middle cerebral artery infarction with alteration of serum NSE, S-100B and endothelin.

Acupuncture may help motor recovery in chronic stroke survivors, but it is unclear whether it is useful for acute or subacute stroke patients. This study aimed to assess the effiency of electroacupuncture on hemiplegic patients caused by acute first-ever middle cerebral artery infarction. Ninety-eight patients with hemiplegia after first-ever middle cerebral artery infarction were divided into the observation group and the control group. Electroacupuncture was applied once daily for three weeks seven days after symptom onset. The motor functions of the limbs and the activities of daily living (ADL) were evaluated by Fugl-Meyer assessment (FMA) and Barthel index (BI). Serum neuron-specific enolase (NSE), soluble protein-100B (S-100B) and endothelin (ET) were quantified before and after treatment.After treatment, the FMA and BI scores were improved in comparison to before treatment scores in the same group (P<0.01 or P<0.05), with a more significant improvement in the observation group (with electroacupuncture) than in the control group (P<0.01). After treatments, the amounts of serum NSE, S-100B and ET in the observation group were significantly decreased when compared with those of the control group (P<0.01 or P<0.05). No adverse reactions occurred during electroacupuncture. This study showed that motor functions of the limbs and the activities of daily living in hemiplegic patients caused by acute cerebral infarction were improved significantly after treatment with electroacupuncture and this improvement was associated with reduced serum levels of NSE, S-100B and ET.

Profiles of blood biomarkers in alternating hemiplegia of childhood--increased MMP-9 and decreased substance P indicates its pathophysiology.

Alternating hemiplegia of childhood (AHC) is a rare disorder characterized by repeated plegic attacks, movement disorders, autonomic phenomena, and developmental delay. To obtain insights into the pathophysiology of AHC, we determined the concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of MMP-1 (TIMP-1), calcitonin gene-related peptide (CGRP), and substance P (SP) in the serum/plasma of AHC patients (n=6) and control subjects (n=11) by performing enzyme-linked immunosorbent assay (ELISA). Decreased levels of serum SP (382±161 pg/ml), increased levels of plasma MMP-9 (111.0±99.3 ng/mL) and increased MMP-9/TIMP-1 ratio (0.65±0.44) were revealed, compared to those in control subjects (SP: 620±223 pg/mL, p<0.05; MMP-9: 33.5±20.3 ng/mL, p<0.05; MMP-9/TIMP-1 ratio 0.21±0.09, p<0.005). Serum CGRP levels in AHC patients (32.6±14.4 pg/mL) were comparable to those in control subjects (37.0±17.0 pg/mL). Increased MMP-9 levels may be linked to the vascular insult and is common in migraineurs. However, because AHC patients showed different changes in SP and CGRP levels compared to those shown by migraineurs, these results suggest that AHC has a pathomechanism different from the hypothesis of trigeminovascular theory. Decreased SP may represent the autonomic dysfunction in AHC, for which an etiology with progressive neuronal damage can be hypothesized.

[Sequential acupuncture method for treatment of apoplexy hemiplegia and its effects on plasma ET-1 and NO levels].

OBJECTIVE: To observe clinical therapeutic effect of sequential acupuncture method on apoplexy hemiplegia and to probe into the mechanism. METHODS: One hundred and forty-four cases of apoplexy hemiplegia were randomly divided into a treatment group treated with sequential acupuncture method and a control group treated with traditional acupuncture, 72 cases in each group. After treatment for 3 months, their clinical therapeutic effects were observed and plasma endothelin-1 (ET-1) and nitric oxide (NO) levels were detected. RESULTS: The treatment group in the improvement of the nerve function-deficiency, total life ability and clinical overall effect, and the course of recovery, decreasing of ET-1 level and increasing of NO level was superior to the control group (P < 0.05, P < 0.01), the shorter the course, the better the therapeutic effect. CONCLUSION: The sequential acupuncture method has an obvious therapeutic effect on apoplexy hemiplegia, and it can decrease plasma ET-1 level and increase NO level. It is an effective therapy for apoplexy hemiplegia.

Use of therapeutic plasma exchange in the management of acute hemorrhagic leukoencephalitis: a case report and review of the literature.

BACKGROUND: Acute hemorrhagic leukoencephalitis (AHLE) is a rare, fatal, central nervous demyelinating disease characterized by a rapid fulminant clinical course. Successful management requires early diagnosis, aggressive management of cerebral edema, and immunosuppression. Therapeutic plasma exchange (TPE) is infrequently used and commences after initial management fails. CASE REPORT: A 31-year-old man presented with right arm weakness, whose symptoms rapidly progressed to hemiplegia and aphasia. The patient was initially managed with glucocorticosteroids. Decompressive craniotomy and brain biopsies were performed when his intracranial pressure increased. Brain biopsy findings were consistent with AHLE. Mycoplasma pneumonia immunoglobulin G and immunoglobulin M serologies revealed recent infection. Despite surgical and medical management, he decompensated on Day 11, and TPE was initiated. The patient received a total of 10 TPE treatments. On the fourth day of TPE treatment, he was extubated. Twenty-one days after TPE began, he was ambulating with near normal muscle strength and was discharged. Four months after initial presentation, the patient has normal strength and is working full-time. CONCLUSIONS: AHLE has a fulminant course requiring accurate and rapid diagnosis. Successful therapy requires aggressive management of intracranial pressure and immunosuppression. Two other reports of AHLE document successful management with TPE. Each of these patients survived with minimal neurologic impairments. Given the likely immune-mediated nature of this disease, combined treatment of steroids, surgery, and TPE may lead to shorter hospital stays and improved neurologic outcomes. Clinical studies are needed to further study the effect of TPE on neurologic outcome in AHLE.

Hypercytokinemia in hemiconvulsions-hemiplegia syndrome associated with dual infection with varicella zoster and Epstein-Barr viruses.

Hemiconvulsions-hemiplegia (HH) syndrome is an acquired condition in which hemiplegia develops after a preceding febrile unilateral status epilepticus in a previously healthy child. Although viral encephalitis or vascular diseases may be the underlying etiology, the pathogenesis remains unknown in the majority of cases. We measured both plasma and cerebrospinal fluid cytokine levels in a girl with HH syndrome, and found elevated plasma concentrations of soluble interleukin-2 receptor and tumor necrosis factor-alpha, and a slightly increased plasma level of interleukin-6. Furthermore, she had a high serum concentration of soluble E-selectin, which is a marker of inflammatory endothelial activation. These findings suggest that proinflammatory cytokine-induced cerebrovascular endothelial injury could play a role in the pathogenesis of HH syndrome.

Plasma concentrations of C-reactive protein and fibrinogen in ischaemic stroke.

This study investigated how fibrinogen and C-reactive protein (CRP) levels change in response to neural damage occurring after ischaemia, and the relationship between the distribution of the arterial lesion, the disease prognosis and the levels of these substances. Fibrinogen and CRP levels were measured in blood samples obtained from 83 patients admitted to hospital within 72 h of a first ischaemic stroke. The patients were evaluated clinically with the Glasgow Outcome Scale (GOS), and results were compared with 43 age-matched controls. The fibrinogen and CRP levels in unconscious patients with hemiparesis or hemiplegia were higher than those in conscious hemiplegic patients. Also, the difference in GOS values between the unconscious patients with hemiparesis or hemiplegia and conscious patients with hemiparesis or hemiplegia was statistically significant. Patients with large infarcts in the median cerebral artery and anterior cerebral artery had higher fibrinogen and CRP concentrations than the control group. In conclusion, fibrinogen and CRP may be important measures for determining the prognosis and outcome in patients following ischaemic stroke.

Serum beta2-microglobulin reflects increased bone resorption in immobilized stroke patients.

OBJECTIVE: The so-called bone-derived growth factor, beta2-microglobulin, has a regulatory function in bone metabolism by stimulating osteoclast activity. We undertook this study because osteoclast activity is known to be enhanced in patients with immobilized stroke, suggesting that their beta2-microglobulin concentrations may be increased. DESIGN: We studied 79 patients with acute stroke hemiplegia, including 36 men and 43 postmenopausal women ranging in age between 51 and 70 yr. RESULTS: The mean Barthel Index was 43 and 42 for men and women, respectively. The serum beta2-microglobulin concentration was increased in male and female patients, compared with the findings of 44 age-matched control subjects, and the serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen was also increased in male and female patients, compared with the findings of the control subjects. Serum concentrations of pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen correlated negatively with Barthel Index scores in both genders, indicating increased bone resorption caused by immobilization in these patients. Linear regression analysis revealed a positive correlation between beta2-microglobulin and pyridinoline cross-linked carboxyterminal telopeptide of type 1 collagen in both genders. CONCLUSIONS: These findings suggest that beta2-microglobulin reflects osteoclastic activity in response to stroke-induced immobilization in both genders. Beta2-microglobulin is a useful indicator of bone resorption in patients with immobilized stroke.

Beneficial effect of intermittent cyclical etidronate therapy in hemiplegic patients following an acute stroke.

Significant decreases in bone mineral density (BMD) occur on the hemiplegic side in chronic stroke patients, which correlate with the degree of paralysis and hypovitaminosis D. In this double-blind, randomized, and prospective study of 98 patients with hemiplegia involving both an upper and lower extremity (55 males and 53 females; mean age, 71.4 +/- 0.6 years) after an acute stroke, 49 were given etidronate for 56 weeks and 49 received a placebo. The BMD was measured by computed X-ray densitometry (CXD) of the second metacarpal bone bilaterally. Forty age-matched control subjects were followed for 56 weeks. At baseline, both groups had 25-hydroxyvitamin D [25(OH)D] insufficiency, increased serum ionized calcium and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and low serum concentrations of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D], suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1,25(OH)2D. The BMD on the hemiplegic side decreased by 2.3% and 4.8% in the etidronate and placebo groups, respectively (p = 0.0003). After treatment, the serum 1,25(OH)2D concentration increased by 62.2% in the etidronate group and decreased by 12.4% in the placebo group. The etidronate group had significant decreases in the serum ionized calcium and ICTP and increases in PTH and bone Gla protein (BGP), whereas the placebo group had higher serum calcium and ICTP concentrations but stable PTH. These results suggest that etidronate can prevent decreases in the BMD in hemiplegic stroke patients because it decreases the serum calcium through inhibition of bone resorption and causes a subsequent increase in the serum 1,25(OH)2D concentration.

Influence of immobilization upon calcium metabolism in the week following hemiplegic stroke.

Hip fractures on the paretic side are a serious post-stroke complication and may result from disuse hemiosteopenia, hypovitaminosis D, and an increasing risk of falls. To evaluate short-term immobilization effects, we assessed calcium metabolism in 89 patients 1 week after the hemiplegic stroke and in 36 controls. Patient activity was rated using the Barthel index (BI). Sera from stroke patients and control subjects were assayed for ionized calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), 1, 25-dihydroxyvitamin D (1,25-(OH)(2)D), bone Gla protein (BGP; a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker). Patients' serum concentrations of ionized calcium and ICTP were higher than in controls and correlated negatively with BI; their BGP concentrations were low, correlating positively with BI. Concentrations of serum 25-OHD, 1,25-(OH)(2)D, and PTH also were low; serum 25-OHD was at a deficient level (<10 ng/ml) in nine patients (10%), an insufficient level (10-20 ng/ml) in 56 (63%), and a sufficient level (>20 ng/ml) in only 24 (27%). PTH correlated negatively with calcium and 1,25-(OH)(2)D. Hypovitaminosis D is common in acute stroke patients. Immobilization from acute hemiplegia can increase bone resorption and serum calcium, and inhibit PTH secretion and 1,25-(OH)(2)D production to add to the effects of hypovitaminosis D.

Vitamin K deficiency and osteopenia in disuse-affected limbs of vitamin D-deficient elderly stroke patients.

Bone mineral density is reduced in stroke patients on the hemiplegic and contralateral sides, reflecting a degree of paralysis and vitamin D deficiency. Because the deficiency of vitamin K, a factor essential for site-specific carboxylation of bone Gla protein, is also associated with reduced bone mineral density, an additional contribution of vitamin K to bone changes was assessed in 168 elderly patients with long-standing post-stroke hemiplegia and hypovitaminosis D. Sera were analyzed to relate vitamin K1 concentrations to bone-related biochemical indexes and bone mineral density measured by radiodensitometry of the second metacarpal. Bone mineral density was lower on both sides in patients than in the 56 controls (P < 0.02). Serum vitamin K1 concentrations, which correlated positively with bone Gla protein concentrations (P < 0.0001), were lower in patients (0.48 +/- 0.47 nmol/L) than controls (1.33 +/- 0.49; P < 0.0001). Serum bone Gla protein and 25-hydroxyvitamin D concentrations were lower in patients than controls (P < 0.0001), whereas ionized Ca concentrations were higher in patients (1.277 +/- 0.041 mmol/L) than controls (1.210 +/- 0.049; P < 0.0001), correlating with the Barthel index. Multivariate linear regression identified vitamin K1, bone Gla protein, 25-hydroxyvitamin D, ionized calcium, and the Barthel index as independent bone mineral density determinants on the hemiplegic side and 25-hydroxyvitamin D, calcium, and the Barthel index on the intact side. Immobilization and vitamin K deficiency had stronger osteopenic effects on the hemiplegic side than contralaterally.

Effect of immobilization upon renal synthesis of 1,25-dihydroxyvitamin D in disabled elderly stroke patients.

A 1,25-dihydroxyvitamin D [1,25-(OH)2D] deficiency and immobilization-related increased serum calcium concentration have been observed in hemiplegic stroke patients. To elucidate the influence of increased serum calcium concentration on bone metabolism, we measured serum biochemical indices and bone mineral density (BMD) in the second metacarpals of 170 elderly subjects with hemiplegic stroke and 72 age-matched healthy controls. Serum concentrations of 25-hydroxyvitamin D [25-(OH)D], 1,25-(OH)2D, ionized calcium, intact parathyroid hormone (PTH), intact bone Gla protein (BGP), and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were measured. An increased serum calcium concentration (mean 2.543 mEq/L) was observed in this population and correlated negatively with the Barthel index (mean 66), indicating immobilization-induced bone resorption with consequent increased serum calcium. Decreased serum concentrations of 1,25-(OH)2D (mean 25.0 pg/mL) and serum 25-OHD concentration (mean 11.6 ng/mL) were noted. Serum PTH was not increased (mean 34.8 pmol/L). Serum levels of BGP were decreased significantly, whereas serum ICTP concentrations were elevated (mean 15.2 ng/mL). A strong negative correlation was seen between the serum calcium concentration and 1,25-(OH)2D (p < 0.0001). BMD of the second metacarpal in patients was decreased significantly compared with control subjects and highly correlated with 25-(OH)D and 1,25-(OH)2D concentrations. Immobilization-related increased serum calcium levels may inhibit PTH secretion, and thus 1,25-(OH)2D production. In addition, 25-(OH)D insufficiency also may contribute to decreased concentration of 1,25-(OH)2D.

Moderate ovarian hyperstimulation syndrome complicated by deep cerebrovascular thrombosis.

This report describes two cases that developed moderate ovarian hyperstimulation syndrome (OHSS) without evidence of haemoconcentration. Both patients developed serious cerebrovascular thrombosis resulting in hemiparesis, and recovered after treatment with anticoagulants. This report emphasizes that other factors may contribute to vascular thrombosis, and illustrates that cerebrovascular accidents may complicate even moderate OHSS.

Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients.

Significant reduction in bone mineral density (BMD) occurs in stroke patients on the hemiplegic and contralateral sides, correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition, and increasing the risk of hip fracture. We evaluated the efficacy of vitamin K2 (menatetrenone: menaquinone-4; MK-4) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients. In a random and prospective study, of 108 hemiplegic patients following stroke, 54 received 45 mg menatetrenone daily (MK-4 group, n = 54) for 12 months, and the remaining 54 (untreatment group) did not. Nine patients excluded from the study. The BMD in the second metacarpals and serum indices of bone metabolism were determined. BMD on the hemiplegic side increased by 4.3% in the MK-4 group and decreased by 4.7% in the untreated group (p < 0.0001), while BMD on the intact side decreased by 0.9% in the MK-4 group and by 2.7% in the untreated group (p < 0.0001). At baseline, patients of both groups showed vitamin D and K1 deficiencies, high serum levels of ionized calcium, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), and low levels of parathyroid hormones (PTH) and bone Gla proteins (BGP), indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1, 25-dihydroxyvitamin D (1, 25-[OH]2D) and compensatory PTH secretion. Both vitamins K1 and K2 increased by 97.6% and 666.9%, respectively, in the MK-4 group. Correspondingly, a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group, in association with a simultaneous increase in both PTH and 1, 25-[OH]2D. One patient in the untreated group suffered from a hip fracture, compared with none in the MK-4 group. The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration, and it also can decrease calcium levels through inhibition of bone resorption, resulting in an increase in 1, 25-[OH]2D concentration.

Increased bone resorption during the first year after stroke.

BACKGROUND AND PURPOSE: Significant bone mineral density (BMD) reduction occurs in stroke patients on the hemiplegic side compared with the intact side. To elucidate the pathogenesis of hip fractures in this population, we measured serum markers of bone metabolism and BMD in the stroke patients within 1 year (early group) and between 1 and 2 years after onset of hemiplegia (long-term group). METHODS: Sera were collected from 51 patients from the early group and 93 patients from the long-term group. All patients had hemiplegia. Sera were assayed for pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker) and bone Gla protein (a bone formation marker). The z score of BMD was determined in both second metacarpals. RESULTS: Serum ICTP concentrations (ng/mL) were higher in the early group (15.4+/-4.1) than in the long-term group (6.7+/-4.4). Bone Gla protein was normal or low in both groups. Multiple regression analysis identified Barthel Index, degree of hemiplegia, and illness duration as independent determinants of ICTP in the early group, whereas Barthel Index, degree of hemiplegia, and serum calcium were determinants of ICTP in the long-term group. There were statistically significant correlations between the z score of the hemiplegic side and age, Barthel Index, degree of hemiplegia, illness duration, 25-hydroxyvitamin D (25-OHD), and ICTP in the early group and between the z score and degree of hemiplegia and 25-OHD level in the long-term group. CONCLUSIONS: The pathogenesis of reduced BMD differed between the early and long-term stroke groups. These results suggest that in the early group, increased bone resorption caused by immobilization was responsible for osteopenia on the hemiplegic side, whereas the degree of hemiplegia and 25-OHD level were the determinants of osteopenia in the long-term group.

Transcutaneous oxygen measurement in stroke: circulatory disorder of the affected leg?

OBJECTIVE: To identify variances in the microcirculation of the affected leg of stroke patients and to correlate them with a number of variables that are clinically associated with a possible circulatory disorder ("cold leg"). DESIGN: Survey. SETTING: Large regional (tertiary care) rehabilitation center. PATIENTS: From 93 acute, first-ever stroke patients admitted for stroke rehabilitation, 10 individuals were selected. Patients with vascular or cardiopulmonary pathology and severe cognitive or speech impairments were excluded. MAIN OUTCOME MEASURES: A clinical assessment of the following variables was performed: subjective complaints of the affected leg, medication, walking performance, degree of lower-leg edema, trophic pathology, voluntary muscle activity of the dorsal flexors of the affected foot, and the degree of spasticity of the calf muscles. The microcirculation of the affected leg was registered via transcutaneous oxygen measurement (TcPO2). RESULTS: The clinical picture associated with a circulatory disorder ("cold leg") was partially and modestly present in seven patients. The TcPO2 values showed no differences between the paretic and nonparetic lower legs, nor did values change in the course of time after stroke: mean 77.9 mmHg (range 42-124) versus 86.1 (41-124) after 8 weeks (n = 10, p = .17); 76.9 (45-96) versus 73.1 (50-96) after 14 weeks (n = 9, p = .38); and 65.8 (44-88) versus 65.8 (37-78) after 20 weeks (n = 8, p = .48). The clinical symptoms could not be objectified in relation to the microcirculation. CONCLUSIONS: In selected stroke patients, no differences were established between microcirculation in both lower legs. TcPO2 measurement does not seem to be a suitable method for clinical research on this topic.

Mechanisms of ischaemic stroke after chickenpox.

Ischaemic stroke is a recognized complication of chickenpox. Seven cases of ischaemic stroke in children after recent varicella infection are discussed in detail to emphasise that there are several mechanisms by which this may arise.