MR imaging with 3D DIR enables increased intracortical lesion detection in the multiple sclerosis brain, as well as improved distinction between juxtacortical and white matter-gray matter lesions.

SummaryAlmost 50% of the cells infiltrating the central nervous system (CNS) of animals with experimental allergic encephalomyelitis (EAE) are macrophages (M(p) . To investigate the role of the M(p in the pathogenesis of EAE, we eliminated Mcp by means of mannosylated liposomes containing dichloromethylene diphosphonate (C12MDP) . C12MDP-containing liposomes injected intravenously eliminate M(p in spleen and liver. Incorporation of mannose into the lipid layers enables the liposomes to pass the blood-brain barrier (BBB). Injections of C12MDP-containing mannose liposomes intravenously shortly before the appearance of clinical signs, markedly suppressed the expression of clinical signs of EAE . This suppression was accompanied by a marked reduction of infiltrated M(p in the CNS. C12MDP-containing liposomes without mannose incorporated had no effect . C12MDP-containing mannosylated liposomes had no effect on plasma corticosterone levels compared with injections of saline; thus, the suppression of expression of EAE was not corticosterone mediated . These results show that the M(p within the CNS play an important role in the pathogenesis of EAE .

High-resolution sonography is an accurate and easily applied test for the diagnosis of UNE. The authors recommend its use in addition to electrodiagnostic studies because it improves the reliability of the diagnosis of UNE.

Disease progression in multiple sclerosis occurs within the interface of glial activation and gliosis. This study aimed to investigate the relationship between biomarkers of different glial cell responses: (i) to disease dynamics and the clinical subtypes of multiple sclerosis; (ii) to disability; and (iii) to cross-validate these findings in a post-mortem study. To address the first goal, 51 patients with multiple sclerosis [20 relapsing remitting (RR), 21 secondary progressive (SP) and 10 primary progressive (PP)] and 51 neurological control patients were included. Disability was assessed using the ambulation index (AI), the Expanded Disability Status Scale score (EDSS) and the 9-hole PEG test (9HPT). Patients underwent lumbar puncture within 7 days of clinical assessment. Post-mortem brain tissue (12 multiple sclerosis and eight control patients) was classified histologically and adjacent sites were homogenized for protein analysis. S100B, ferritin and glial-fibrillary acidic protein (GFAP) were quantified in CSF and brain-tissue homogenate by ELISA (enzyme-linked immunosorbent assay) techniques developed in-house. There was a significant trend for increasing S100B levels from PP to SP to RR multiple sclerosis (P < 0.05). S100B was significantly higher in RR multiple sclerosis than in control patients (P < 0.01), whilst ferritin levels were significantly higher in SP multiple sclerosis than in control patients (P < 0.01). The S100B : ferritin ratio discriminated patients with RR multiple sclerosis from SP, PP or control patients (P < 0.05, P < 0.01 and P < 0.01, respectively). Multiple sclerosis patients with poor ambulation (AI > or =7) or severe disability (EDSS >6.5) had significantly higher CSF GFAP levels than less disabled multiple sclerosis or control patients (P < 0.01 and P < 0.001, respectively). There was a correlation between GFAP levels and ambulation in SP multiple sclerosis (r = 0.57, P < 0.01), and between S100B level and the 9HPT in PP multiple sclerosis patients (r = -0.85, P < 0.01). The post-mortem study showed significantly higher S100B levels in the acute than in the subacute plaques (P < 0.01), whilst ferritin levels were elevated in all multiple sclerosis lesion stages. Both GFAP and S100B levels were significantly higher in the cortex of multiple sclerosis than in control brain homogenate (P < 0.001 and P < 0.05, respectively). We found that S100B is a good marker for the relapsing phase of the disease (confirmed by post-mortem observation) as opposed to ferritin, which is elevated throughout the entire course. GFAP correlated with disability scales and may therefore be a marker for irreversible damage. The results of this study have broad implications for finding new and sensitive outcome measures for treatment trials that aim to delay the development of disability. They may also be considered in future classifications of multiple sclerosis patients.

The authors conducted a randomized, double-blind, placebo-controlled, twofold crossover study in 16 patients with MS who presented with severe spasticity to investigate safety, tolerability, and efficacy of oral Delta(9)-Tetrahydrocannabinol (THC) and Cannabis sativa plant extract. Both drugs were safe, but adverse events were more common with plant-extract treatment. Compared with placebo, neither THC nor plant-extract treatment reduced spasticity. Both THC and plant-extract treatment worsened the participant's global impression.

The aim of this study was to determine possible correlations between the clinical characteristics, electrophysiological features, and sonographic ulnar-nerve diameter in patients with ulnar neuropathy at the elbow (UNE). We prospectively performed clinical, electrodiagnostic, and sonographic studies in 102 patients having either purely sensory signs (35%) or sensorimotor signs (65%) of UNE. Nerve conduction studies had a sensitivity of 78%, and the addition of sonography increased this to 98%. The diagnostic value of both tests was not different among cases with and without motor deficit. Motor studies with recording from the abductor digiti minimi and first dorsal interosseous muscles were equally sensitive for the detection of conduction block or velocity slowing across the elbow, but the combination yielded more positive cases than when only one study was performed. There were modest negative correlations between the electrodiagnostic parameters and the sonographic ulnar-nerve diameter. Electrodiagnostically and sonographically, there were no significant differences between clinically pure sensory and mixed sensorimotor cases of UNE, except for electrodiagnostic findings suggesting loss of motor axons in cases with motor signs. Almost half the patients with only sensory signs had electromyographic evidence of motor axonal loss. We conclude that, although UNE is clinically heterogeneous, the electrophysiological and sonographic findings are fairly consistent despite the clinical manifestations.

Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was used to determine metabolite concentrations in the cerebral normal-appearing white matter (NAWM) of 76 patients with multiple sclerosis (MS), and the WM of 25 controls. In NAWM of all MS disease types (primary progressive, relapsing-remitting, and secondary progressive), the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine (tCr) was decreased compared to controls. Remarkably, this was entirely due to an increase of tCr in MS patients, whereas there was no difference in tNAA. Separate quantification of the two tNAA components yielded no significant difference in NAA (N-acetylaspartate), while the concentration of NAAG (N-acetyl-aspartylglutamate) was slightly-but significantly-elevated in MS patients. Myo-inositol (Ins) was strongly increased in MS patients, and choline-containing compounds (Cho) were mildly increased. There were no metabolite differences between disease types, and no correlations with disability scores. The results are supported by measures of spectral quality, which were identical for patients and controls. The cerebral normal-appearing white matter (NAWM) in multiple sclerosis (MS) patients has received much attention in MR research. Although large areas of WM appear normal on conventional T 1 -and T 2 -weighted MR images, several (semi-) quantitative techniques have shown differences with the normal WM of healthy controls. The reported abnormalities suggest the presence of either distinct lesions that are too small to be detected using common pixel sizes and magnetic field strengths, or diffuse disease processes that take place outside the focal lesions.The magnetization transfer ratio (MTR) has been found to be decreased in MS NAWM compared to control WM (e.g., Ref. 1), indicating damage to the macromolecular matrix. In addition, increases have been reported for T 1 and T 2 relaxation times (e.g., Ref.2). The apparent diffusion coefficient (ADC) of water is also increased, which along with observed reductions of the anisotropy as derived from the water diffusion tensor, is suggestive of loss of integrity of WM tracts (e.g., Ref.3).Investigations of MS NAWM using MR spectroscopy (MRS) have reported, among other findings, a decrease in the tNAA/tCr ratio (4,5) (where tNAA [abbreviated in some papers as NAA or NA] indicates total NAA, meaning the summed concentrations of N-acetyl-aspartate [NAA], and N-acetyl-aspartyl-glutamate [NAAG]; and tCr indicates the summed concentrations of creatine and phosphocreatine). Although a decrease of tNAA/tCr is thus a common finding in MS NAWM, there is still controversy about the underlying cause of this phenomenon. On the assumption that tCr is constant, it has been inferred from the decreased ratio that the concentration of tNAA is reduced in MS NAWM in comparison with control WM. Because tNAA is generally regarded as a marker of neuro-axonal viability, a decrease in the concentration of tNAA in MS NAWM could be interpreted as an indication of axonal damage. Some...

Worsening on T25FW or 9HPT has a clinical impact on disability, as perceived by MS patients during daily life functioning.