Background and Purpose-The Barthel Index (BI) and the Modified Rankin Scale (MRS) are commonly used scales that measure disability or dependence in activities of daily living in stroke victims. The objective of this study was to investigate how these scales were used and interpreted in acute stroke trials. Methods-We identified from MEDLINE the major efficacy trials with neuroprotective drugs, thrombolytic drugs, and anticoagulants in acute ischemic stroke published between January 1995 and December 1998. We selected those trials that used the BI and/or MRS as outcome parameters. Results-Fifteen trials fulfilling the inclusion criteria were identified. The BI was used in 13 and the MRS in 8. In 4 trials mean and median scores of the BI were used, and in 1 trial median scores of the MRS were compared. Primary end points included the BI in 7, the MRS in 6, and both the BI and MRS in 3. With regard to the BI, a variety of sum scores between 50 and 95 were used as cutoff scores to define favorable outcome. Favorable outcome on the MRS was defined as either Յ1 or Յ2. Conclusions-Among the efficacy trials in acute stroke, we found remarkable differences in the choice of primary end points and in the definition of favorable outcome on both the BI and MRS. This lack of consensus strongly hinders the design, interpretation, and comparison of acute stroke trials. In general, it may be easier to define poor outcome instead of favorable outcome. Poor outcome could be defined if any of the following end points are reached: death, institutionalization due to stroke, MRS Ͼ3, or BI Ͻ60. (Stroke. 1999;30:1538-1541.)

Multiple sclerosis (MS) is a disease of the central nervous system characterized by patchy areas of demyelination, inflammation, axonal loss and gliosis, and a diffuse axonal degeneration throughout the so-called normal-appearing white matter (NAWM). A number of recent studies using perfusion magnetic resonance imaging in both relapsing and progressive forms of MS have shown a decreased perfusion of the NAWM, which does not appear to be secondary to axonal loss. The reduced perfusion of the NAWM in MS might be caused by a widespread astrocyte dysfunction, possibly related to a deficiency in astrocytic beta(2)-adrenergic receptors and a reduced formation of cAMP, resulting in a reduced uptake of K(+) at the nodes of Ranvier and a reduced release of K(+) in the perivascular spaces. Pathologic and imaging studies suggest that ischemic changes might be involved in the development of a subtype of focal demyelinating lesions (type III lesions), and there appears to exist a relationship between decreased white matter perfusion and cognitive dysfunction in patients with MS.

Background: Pregnancy has a well-documented effect on relapses in multiple sclerosis (MS), whereas little is known about the impact of pregnancy and childbirth on the risk of secondary progression. Objective: To investigate the association of parity and secondary progression in women with MS. Methods: The association of the number of births and secondary progression was studied in a hospital-based cohort of 277 women with MS. Data were analysed in a multivariable logistic regression model, with adjustment for possible confounders. Results: Parity was not independently associated with secondary progression, while the factors disease duration (OR per year increase: 1.05, 95% CI 1.03 to 1.09) and use of immunomodulatory treatments (OR 0.23, 95% CI 0.08 to 0.65) were independently associated with secondary progression. Conclusion: We found no evidence that parity influences the risk of secondary progression in MS. Further population-based studies on the association of pregnancy and childbirth on the long-term prognosis of MS are needed.Multiple sclerosis (MS) affects women about twice as often as men. Since MS often begins in early adulthood, the course of the disease overlaps the childbearing years in many women with MS. A number of studies have been concerned with the impact of pregnancy on MS relapses, but little research has been done on the influence of pregnancies on the onset of secondary progression.The pathophysiological mechanisms underlying relapses are focal inflammatory lesions in the central nervous system (CNS). The main pathophysiological mechanism of secondary progression appears to be an ill-understood diffuse neurodegeneration throughout the CNS termed ''axonal degeneration.'' Axonal degeneration may begin early in the disease but becomes apparent as secondary progression when enough axons have degenerated to exhaust the functional reserve capacity of the CNS. Previous studies have shown that relapses occur less frequently during pregnancy, especially during the third trimester, and that there is a rebound effect with an increase in relapse frequency after delivery. 3 These findings have been associated with the rise and fall of oestrogen and progesterone levels over the course of pregnancy and argue for a suppressive effect of these steroid hormones on the inflammatory component of MS. One exploratory crossover trial found evidence for an effect of oral oestriol treatment on the number of enhancing MRI lesions in a group of 12 women with MS. 4 Information about the effect of pregnancy on the development of secondary progression is scarce. We found only one small study suggesting a significantly decreased risk of a progressive course in women who became pregnant after MS onset.5

BackgroundTwo studies using 31P-magnetic resonance spectroscopy (MRS) reported enhanced phosphocreatine (PCr) levels in normal appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but this finding could not be properly explained.Methodology/Principal FindingsWe performed 31P-MRS and 1H-MRS in the NAWM in 36 subjects, including 17 with progressive MS, 9 with benign MS, and 10 healthy controls. Compared to controls, PCr/β-ATP and PCr/total 31P ratios were significantly increased in subjects with progressive MS, but not with benign MS. There was no correlation between PCr ratios and the N-acetylaspartate/creatine ratio, suggesting that elevated PCr levels in NAWM were not secondary to axonal loss. In the central nervous system, PCr is degraded by creatine kinase B (CK-B), which in the white matter is confined to astrocytes. In homogenates of NAWM from 10 subjects with progressive MS and 10 controls without central nervous system disease, we measured CK-B levels with an ELISA, and measured its activity with an enzymatic assay kit. Compared to controls, both CK-B levels and activity were decreased in subjects with MS (22.41 versus 46.28 µg/ml; p = 0.0007, and 2.89 versus 7.76 U/l; p<0.0001).Conclusions/SignificanceOur results suggest that PCr metabolism in the NAWM in MS is impaired due to decreased CK-B levels. Our findings raise the possibility that a defective PCr metabolism in astrocytes might contribute to the degeneration of oligodendrocytes and axons in MS.

Our results suggest that in MS patients there is no relationship between reduced CBF in NAWM and impaired axonal mitochondrial metabolism or astrocytic PCr metabolism.

: Studies were carried out on changes in water proton relaxation, Instron parameters, dimethylamine (DMA) content and sensory texture scores during storage of cod mince at [10¡C, [20¡C and [70¡C. The longest transverse proton relaxation time measured by pulsed low-resolution nuclear magnetic resonance (NMR) spectroscopy increased with temperature and duration of frozen storage. These variations in the NMR parameter paralleled changes observed with analytical methods commonly used for evaluating Ðsh texture, ie Instron measurements, as well as dimethylamine and sensory analyses. It is concluded that the NMR method can be an alternative tool to study textural modiÐ-cations of cod during frozen storage.

Our findings indicate that the amount of T2 lesions has a small predictive value for progression of disability in relapsing remitting MS, but has no influence on the rate of progression in progressive MS.

A mildly retarded infant with failure to thrive developed hypoglycaemia, focal seizures, respiratory failure and hemiparesis during a febrile episode at the age of 16 months. A brain scan was initially normal and showed hemilateral focal edema and gliosis at later stages. 3-Methylcrotonyl-CoA carboxylase deficiency was suggested by elevated urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, and confirmed by enzyme assays. The patient was treated with protein restriction and carnitine and remained stable during the following 5 years. Hemiparesis and some developmental delay persisted. In acute focal brain disease, metabolic disorders must be considered. 3-Methylcrotonyl-CoA carboxylase deficiency adds to the list of possible causes of "metabolic stroke".