Purpose: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy controls (HC) using cine phase contrast imaging. Materials and Methods:In all, 67 MS patients (48 relapsing-remitting [RR] and 19 secondary-progressive [SP]), nine patients with clinically isolated syndrome (CIS), and 35 age-and sex-matched HC were examined. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and magnetic resonance imaging (MRI) disease outcomes.Results: Significantly decreased CSF net flow was detected in MS patients compared to HC (À3.7 vs. À7.1 mL/beat, P ¼ 0.005). There was a trend for increased net positive flow between SP, RR, and CIS patients. Altered CSF flow and velocity measures were associated with more severe T1 and T2 lesion volumes, lateral and fourth ventricular volumes, and third ventricular width in MS and CIS patients (P < 0.01 for all). In CIS patients, conversion to clinically definite MS in the following year was related to decreased CSF net flow (P ¼ 0.007). There was a trend between increased annual relapse rate and altered CSF flow/velocity measures in RRMS patients (P < 0.05).Conclusion: CSF flow dynamics are altered in MS patients. More severe clinical and MRI outcomes in RRMS and CIS patients relate to altered CSF flow and velocity measures.

Calcium-dependent protein kinases (CDPKs) in plants typically contain a C-terminal calmodulin-like domain with four EF-hand calcium-binding motifs. We have isolated a carrot somatic embryo cDNA clone which encodes a new, divergent isoform of this family, designated CRK (CDPK-related kinase). The catalytic domain of CRK shares a high degree of homology with the catalytic domains of plant CDPKs (53.5% average identity with its two closest phylogenetic relatives, CDPK431 (carrot) and AK1 (Arabidopsis). However, the C-terminal domain of CRK bears significantly less homology to calmodulin (22.0% identity to barley calmodulin) than other plant CDPKs (38.0% average identity between barley calmodulin and the C-terminal domains of CDPK431 and AK1). This degeneracy also involves the EF-hand motifs of CRK, which have diverged to varying extents. The predicted structure of CRK also contains an extended N-terminal domain 145 amino acids in length possessing a consensus N-myristoylation signal. CRK transcripts are most abundant in somatic embryos, with lesser accumulations in flowers and leaves and lowest levels in roots. Homologous genomic DNA sequences that hybridize with CRK cDNA but not with a carrot CDPK probe have been detected in a variety of higher plant taxa, including monocotyledonous species, suggesting that this CDPK-related kinase is widely conserved among angiosperms.

Background and objectives It is widely accepted that typical acute demyelinating lesions in relapsing–remitting multiple sclerosis (RRMS) exhibit vasogenic edema with increased diffusion, as demonstrated by an increased apparent diffusion coefficient on MRI. In contrast, acute ischemic lesions demonstrate cytotoxic edema with restricted diffusion. Recent reports have documented selected cases of acute demyelinating lesions exhibiting restricted diffusion (ADLRD) in MS. We aimed to assess the morphologies, distributions, signal characteristics and changes over time of nine ADLRD. An additional goal was to obtain clinical correlations and relate our findings to all previously published case reports describing ADLRD. Methods A retrospective case series study was performed at two academic centers. MRI characteristics of nine ADLRD found in six RRMS patients were compared with typical active symptomatic contrast-enhancing lesions with increased or normal diffusion in control RRMS patients. Results The average size of ADLRD was not significantly different from typical lesions. A periventricular location and faint signal on T2-weighted images were significantly more common for ADLRD compared with typical lesions. Two patients with ADLRD on initial MRI exhibited new ADLRD on their follow up scans. Conclusion Our results and review of prior published cases suggest that ADLRD represent a new variant of MS lesion. The restricted diffusion that is a characteristic of ADLRD on MRI is a new challenge in the differential diagnosis of stroke in young adults. The pathogenesis of ADLRD remains to be understood.

We report here a case of progressive tumefactive inflammatory central nervous system (CNS) demyelinating disease in a human immunodeficiency virus (HIV)-seropositive patient treated with highly active antiretroviral therapy (HAART). Biopsy revealed diffuse macrophage and perivascular T-lymphocytic infiltrates with severe demyelination and relative axonal sparing. The disease progressed in a centrifugal fashion, to involve bihemispheric cerebral white matter, with subsequent central necrotic changes and atrophy. Treatment with HAART was discontinued, and inflammatory disease was treated with subcutaneous interferon (IFN)beta-1a. Massive brain edema was controlled with courses of intravenous corticosteroids. Following fulminant monophasic disease, the patient stabilized with no evidence of disease progression over long-term follow up. We propose that immune response reconstituted by HAART can unmask an autoimmune response in susceptible individuals, analogous to the enhanced immune response to the preexisting acquired immunodeficiency syndrome (AIDS) opportunistic infections. Therapeutic options are considered.