CT perfusion quantification of small-vessel ischemic severity

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) abnormalities are previously demonstrated in white matter disease. A gradation of change may exist between patients with mild and more severe white matter disease. An association between blood brain barrier dysfunction, increasing age and white matter disease is also suggested. The purpose of this study was to quantify and correlate white matter disease severity and CT perfusion (CTP)-derived CBF and to determine whether permeability surface abnormality increases with white matter disease severity.MATERIALS AND METHODS: One hundred twenty patients with strokelike symptoms underwent CTP and MR imaging. Of these, 35 patients (15 women, 20 men; age, 66 ± 15.7 years) with rapidly resolving symptoms and normal imaging characteristics consistent with transient ischemic attack were retrospectively reviewed and constituted the study cohort. Two blinded neurologists rated white matter severity, assigning age-related white matter change (ARWMC) scores. Patients were dichotomized a priori into mild and moderate-to-severe. CBF, cerebral blood volume (CBV), mean transit time (MTT), and permeability surface product maps were calculated for periventricular and subcortical white matter regions and average white and gray matter. Associations with white matter severity were tested by uni- and multivariate logistic regression analyses. Receiver operating characteristic analysis was performed.RESULTS: White matter disease was mild in 26 patients and moderate-to-severe in 9. Age was associated with increased likelihood of having moderate-to-severe white matter disease (P = .02). ARWMC correlated with subcortical (r = −0.50, P < .001) and average CBF (r = −0.55, P < .001). White matter severity was associated with subcortical (P = .03) and average (P = .03) white matter CBF, with a trend toward periventricular white matter CBF (P = .05). Uni- and multivariate analysis controlling for the confounding effect of age demonstrated significant association between white matter severity and subcortical (P = .032) white matter CBF. Area under the curve was 0.82. No permeability surface abnormality was found.CONCLUSIONS: CTP-derived subcortical white matter CBF is independently associated with white matter disease severity.

White matter changes are frequent in patients with vascular risk factors, cerebrovascular disease, and cognitive impairment.¹ The pathogenesis is poorly understood. Various histopathologic correlates have been described, including loss of ependyma with gliosis, glial swelling, demyelination, dilated perivascular spaces, lacunar infarcts, spongiosis, arteriolar hyalinosis, amyloid angiopathy, and cyst formation.^2–4 A vascular etiology is strongly suggested, given the frequent association with increasing age, hypertension, stroke, and markers of cellular ischemia, including hypoxia inducible factor, neuroglobulin, and matrix metalloproteinase protein MMP7.^5–7 Other associations include arteriosclerosis,⁸ impaired cerebral autoregulation, hypoperfusion, CSF flow disturbances, and blood-brain barrier (BBB) disruption.^7,9Several validated white matter rating scales allow visual quantification of disease burden on CT or MR imaging. The age-related white matter change (ARWMC) scale can be applied to both CT and MR imaging changes and has been recommended in an attempt to standardize nomenclature in vascular cognitive impairment imaging.¹⁰ White matter lesion visualization is, however, reduced on CT compared with MR imaging. Additionally, visual rating score performances are imperfect and are limited by a ceiling effect. The wide variation in lesion extent with high visual scores results in a lower correlation with clinical symptoms. Whether techniques that provide estimation of white matter hemodynamic parameters independent of CT or MR imaging lesion visualization would better assess severity is unknown but potentially may circumvent these problems.Cerebral blood flow (CBF) abnormalities were previously demonstrated in white matter disease by xenon CT (Xe-CT),¹¹ positron-emission tomography (PET),¹² and MR imaging.^13,14 Correlation of XeCT and single-photon emission tomography (SPECT) hypoperfusion with leukoaraiosis severity was previously described.^11,15 Recent data suggest that hemodynamic alterations precede white matter change.¹⁶ An association between BBB dysfunction, increasing age, dementia, and white matter disease is suggested, with parenchymal gadolinium-diethylene-triamine pentaacetic acid leakage shown in elderly patients with diabetes.¹⁷ Furthermore, microvascular changes, BBB dysfunction, and microglial and astroglial cell activation are reported in primates with cognitive decline.¹⁸ Progress in cross-sectional CT imaging technology allows quantification of absolute cerebral hemodynamic parameters with greater resolution than MR imaging or SPECT-based techniques. CT perfusion (CTP) is cheaper, faster, and more widely available than MR imaging, SPECT, or Xe-CT techniques. CTP is widely used in the evaluation of patients with stroke, but no previous study has examined the relationship between CTP-derived hemodynamic variables and white matter disease severity. The purpose of this study was to test the ability of CTP-derived hemodynamic parameters, including CBF, cerebral blood volume (CBV), mean transit time (MTT), and BBB permeability surface product to quantify white matter disease severity. Our hypothesis was that CTP-derived hemodynamic parameters and, in particular, CBF correlate with and may be used to quantify white matter disease severity. Furthermore, we hypothesized that permeability surface is expected to increase with greater white matter disease severity.     

Cannabinoids prevent the differential long‐term effects of exposure to severe stress on hippocampal‐ and amygdala‐dependent memory and plasticity

Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal‐dependent memory is compromised while amygdala‐dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long‐term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light‐dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long‐term potentiation (LTP) in the CA1, (iii) impaired hippocampal‐dependent short‐term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala‐dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55‐212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal‐ and amygdala‐dependent processes. Moreover, the effects of WIN55‐212,2 and URB597 on Ext and acoustic startle were prevented by co‐administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55‐212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1 receptors, in the opposite effects of severe stress on memory and plasticity in the hippocampus and amygdala.     

Frontal fibrosing alopecia update

Frontal fibrosing alopecia(FFA) is a recently described form of primary cicatricial alopecia, characterized by progressive recession of the frontotemporal hairline and eyebrow loss, occurring predominantly in postmenopausal women. The incidence of FFA has increased significantly during the last decade and we may be facing an epidemic of the disease. Because this condition causes permanent hair loss, prompt diagnosis and treatment are essential for obtaining optimal outcome. This article reviews existing knowledge on epidemiology, etiopathogenesis, clinico-histological features, diagnosis,and treatment modalities of FFA.     

Purification of Biologically Active Globin Messenger RNA by Chromatography on Oligothymidylic acid-Cellulose

A convenient technique for the partial purification of large quantities of functional, poly(adenylic acid)-rich mRNA is described. The method depends upon annealing poly(adenylic acid)-rich mRNA to oligothymidylic acid-cellulose columns and its elution with buffers of low ionic strength. Biologically active rabbit globin mRNA has been purified by this procedure and assayed for its ability to direct the synthesis of rabbit globin in a cell-free extract of ascites tumor. Inasmuch as various mammalian mRNAs appear to be rich in poly(adenylic acid) and can likely be translated in the ascites cell-free extract, this approach should prove generally useful as an initial step in the isolation of specific mRNAs.     

Subcutaneous granuloma annulare mimicking dermatomyositis

We present three children who presented with papules and plaques over the knuckles, mimicking Gottron's papules of juvenile dermatomyositis, as well as subcutaneous nodules over the joints of the extremities that were initially thought to represent calcinosis cutis. However, thorough clinical and laboratory evaluation, as well as imaging, failed to support this diagnosis. Skin biopsies were consistent with a diagnosis of subcutaneous granuloma annulare. This unique phenotype of granuloma annulare should be recognized in order to prevent erroneous diagnosis and treatment.