Maria Matheus

Antagonism of non-NMDA receptors in the dorsal periaqueductal grey induces anxiolytic effect in the elevated plus maze

Abstract Microinjections of glutamate into the dorsal periaqueductal grey (DPAG) of rats induce flight behavior, and blockade of glutamate NMDA receptors in the same region increases exploratory behavior of rats tested on the elevated plus maze. To investigate a possible role of other glutamate receptors in the DPAG on anxiety modulation, rats (n = 6–10) received microinjections into this structure of CNQX (1 and 3 nmol/0.5 μl), an AMPA/kainate antagonist, or GDEE (80 or 160 nmol/0.5 μl), a non-selective glutamate antagonist, and were tested on the elevated plus-maze, an ethologically based animal model of anxiety. Both drugs increased the percentage of entries into open arms, as compared to rats receiving vehicle, without changing the number of enclosed arm entries. Injections of the active compounds outside the DPAG were not effective. The anxiolytic effect of CNQX (3 nmol/0.5 μl) was not reversed by glycine (10 nmol/ 0.5 μl), injected into the DPAG 5 min after CNQX administration. These results suggest that, in addition to NMDA receptors, non-NMDA glutamate receptors may also modulate anxiety in the DPAG.

Anxiolytic effect of glycine antagonists microinjected into the dorsal periaqueductal grey

To investigate if blockade of the modulatory glycine site of NMDA receptors in the dorsal periaqueductal grey (DPAG) would produce anxiolytic effects, groups of 9–14 rats received microinjections into this structure of 7-chloro-kynurenic acid (7-Cl-KY, 4 and 8 nmol) or 3-amino-1-hydroxypyrrolid-2-one (HA-966, 30 or 100 nmol), two selective antagonists at the strychnine-insensitive glycine modulatory site, and were submitted to the elevated plus-maze, an ethologically based animal model of anxiety. Both drugs increased the percentage of entries and of time spent in open arms as compared to rats receiving isotonic saline. Injections of the active compounds outside the DPAG were not effective. In another experiment microinjections of 7-Cl-KY (8 nmol) and HA-966 (100 nmol) into the DPAG raised the threshold of aversive electrical stimulation of the rat DPAG. These results indicate that microinjections of 7-Cl-KY and HA-966 into the DPAG cause anxiolytic effects in two different models of anxiety and support the proposal that NMDA-mediated neurotransmission in the DPAG may be related to anxiety and panic.

Infarct patterns, collaterals and likely causative mechanisms of stroke in symptomatic intracranial atherosclerosis.

Background: There are limited data on the specific mechanisms of stroke in patients with intracranial atherosclerotic stenosis (ICAS). We undertook this study to describe infarct patterns and likely mechanisms of stroke in a large cohort of patients with ICAS, and to evaluate the relationship of these infarct patterns to angiographic features (collaterals, stenosis location and stenosis severity). Methods: We evaluated infarct patterns in the territory of a stenotic intracranial artery on neuroimaging performed at baseline and during follow-up if a recurrent stroke occurred in patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We defined the likely mechanism of stroke (artery-to-artery embolism, perforator occlusion, hypoperfusion or mixed) according to the site of ICAS and based on the infarct patterns on neuroimaging. Collaterals were assessed using American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grades, and stenosis severity using the WASID trials measurement technique. We evaluated the association of infarct patterns with angiographic features using χ2 tests. Results: The likely mechanisms of stroke based on the infarct patterns at baseline in the 136 patients included in the study were artery-to-artery embolism (n = 69; 50.7%), perforator occlusion (n = 34; 25%), hypoperfusion (n = 12; 8.8%) and mixed (n = 21; 15.5%). Perforator-occlusive infarcts were more frequent in the posterior circulation, and mixed patterns were more prevalent in the anterior circulation (both p < 0.01). Most of the mixed patterns in the anterior circulation combined small pial or scattered multiple cortical infarcts with infarcts in border-zone regions, especially the cortical ones. Isolated border-zone infarcts were not significantly associated with a poor grading for collaterals or the severity of stenosis. Among 47 patients with a recurrent infarct during follow-up, the infarct patterns suggested an artery-to-artery embolic mechanism in 29 (61.7%). Conclusions: Artery-to-artery embolism is probably the most common mechanism of stroke in both the anterior and the posterior circulations in patients with ICAS. An extension of intracranial atherosclerosis at the site of stenosis into adjacent perforators also appears to be a common mechanism of stroke, particularly in the posterior circulation, whereas hypoperfusion as the sole mechanism is relatively uncommon. Further research is important to accurately establish the specific mechanisms of stroke in patients with ICAS, since preliminary data suggest that the underlying mechanism of stroke is an important determinant of prognosis.

Meningovascular Syphilis With Fatal Vertebrobasilar Occlusion

We report the case of a young patient with meningovascular syphilis who suffered fatal vertebrobasilar occlusion despite thrombolytic treatment and endovascular interventions. A 35-year-old man without any known medical history presented with an acute ischemic stroke and was initially treated with intravenous tissue plasminogen activator. He was then transferred to the stroke center, where he underwent endovascular recanalization of his occluded vertebrobasilar system. Despite initial successful recanalization, he suffered recurrent vertebrobasilar occlusion, and a second endovascular treatment attempt was unsuccessful. He subsequently developed a pontine hemorrhage and acute hydrocephalus and died secondary to transtentorial herniation. Laboratory findings were suggestive of prior spirochetal infection, and autopsy revealed necrotizing vasculitis and extensive adventitial inflammation involving the basilar and vertebral arteries, supporting the diagnosis of meningovascular syphilis.

Redefining the Pediatric Phenotype of X-Linked Monocarboxylate Transporter 8 (MCT8) Deficiency: Implications for Diagnosis and Therapies.

X-linked monocarboxylate transporter 8 (MCT8) deficiency results from a loss-of-function mutation in the monocarboxylate transporter 8 gene, located on chromosome Xq13.2 (Allan-Herndon-Dudley syndrome). Affected boys present early in life with neurodevelopment delays but have pleasant dispositions and commonly have elevated serum triiodothyronine. They also have marked axial hypotonia and quadriparesis but surprisingly little spasticity early in their disease course. They do, however, have subtle involuntary movements, most often dystonia. The combination of hypotonia and dystonia presents a neurorehabilitation challenge and explains why spasticity-directed therapies have commonly produced suboptimal responses. Our aim was to better define the spectrum of motor disability and to elucidate the neuroanatomic basis of the motor impairments seen in MCT8 deficiency using clinical observation and brain magnetic resonance imaging (MRI) in a cohort of 6 affected pediatric patients. Our findings identified potential imaging biomarkers and suggest that rehabilitation efforts targeting dystonia may be more beneficial than those targeting spasticity in the prepubertal pediatric MCT8 deficiency population.

LIS1 duplication: expanding the phenotype.

Disruptions to LIS1 gene expression result in neuronal migration abnormalities. LIS1 heterozygosity is a significant cause of lissencephaly, while overexpression has recently been noted in cases of microcephaly, ventriculomegaly, and dysgenesis of the corpus callosum with normal cortical gyration. We report a partial LIS1 duplication in a child with microcephaly, neurodevelopmental delays, and profound white matter atrophy in the absence of overt lissencephaly. The duplicated genetic segment was contained entirely within the first intron of LIS1, a segment that often contains inducers of transcription. Normal gyral patterns with mild volume loss were observed at birth. Follow-up cranial imaging revealed further white matter loss, diminished sulcation, and ventriculomegaly, suggesting expanding hydrocephalus ex vacuo. The radiographic pattern has not been documented in the presence of a LIS1 gene abnormality, and suggests that altered expression of LIS1 has wider phenotypic manifestations than currently defined.

Behavioral effects of "vehicle" microinjected into the dorsal periaqueductal grey of rats tested in the elevated plus maze.

To investigate the behavioral effects of different vehicles microinjected into the dorsal periaqueductal grey (DPAG) of male Wistar rats, weighing 200-250 g, tested in the elevated plus maze, animals were implanted with cannulas aimed at this structure. One week after surgery the animals received microinjections into the DPAG of 0.9% (w/v) saline, 10% (v/v) dimethyl sulfoxide (DMSO), 2% (v/v) Tween-80, 10% (v/v) propylene glycol, or synthetic cerebrospinal fluid (CSF). Ten min after the injection (0.5 microliters) the animals (N = 8-13/group) were submitted to the elevated plus maze test. DMSO significantly increased the number of entries into both the open and enclosed arms when compared to 0.9% saline (2.7 +/- 0.8 and 8.7 +/- 1.3 vs 0.8 +/- 0.3 and 5.1 +/- 0.9, respectively. Duncan test, P < 0.05), and tended to increase enclosed arm entries as compared to 2% Tween-80 (8.7 +/- 1.3 vs 5.7 +/- 0.9, Duncan test, P < 0.10). In a second experiment no difference in plus maze exploration was found between 0.9% saline-or sham-injected animals (N = 11-13/group). These results indicate that intra-DPAG injection of some commonly used vehicles such as DMSO, saline or Tween-80 affects the exploratory activity of rats exposed to the elevated plus maze in statistically different manners.

Current Radiographic Iodinated Contrast Agents

Millions of radiologic examinations requiring the use of iodinated contrast are performed yearly in North America. Triiodobenzoic acid, the contrast agent molecule currently in use, is a benzene ring covalently bonded to the 3 iodine atoms. Iodinated contrast media can be divided in 4 categories: ionic monomers, ionic dimers, nonionic monomer, and nonionic dimers. Currently, second- and third-generation nonionic low-osmolar and iso-osmolar contrast media are used in clinical practice. The search for a safer and more effective iodinated contrast agents remains an ongoing challenge and important research topic.

Practical Implications for an Effective Radiology Residency Quality Improvement Program for Milestone Assessment

Utilization of a radiology resident-specific quality improvement (QI) program and curriculum based on the Accreditation Council for Graduate Medical Education (ACGME) milestones can enable a programs assessment of the systems-based practice component and prepare residents for QI implementation post graduation. This article outlines the development process, curriculum, QI committee formation, and resident QI project requirements of one institutions designated radiology resident QI program. A method of mapping the curriculum to the ACGME milestones and assessment of resident competence by postgraduate year level is provided. Sample projects, challenges to success, and lessons learned are also described. Survey data of current trainees and alumni about the program reveal that the majority of residents and alumni responders valued the QI curriculum and felt comfortable with principles and understanding of QI. The most highly valued aspect of the program was the utilization of a resident education committee. The majority of alumni responders felt the residency quality curriculum improved understanding of QI, assisted with preparation for the American Board of Radiology examination, and prepared them for QI in their careers. In addition to the survey results, outcomes of resident project completion and resident scholarly activity in QI are evidence of the success of this program. It is hoped that this description of our experiences with a radiology resident QI program, in accordance with the ACGME milestones, may facilitate the development of successful QI programs in other diagnostic radiology residencies.

RADIATION DOSE AND IMAGE QUALITY IN PEDIATRIC HEAD CT

Our goal was to define a pediatric head CT protocol able to provide images of diagnostic quality, using the least amount of radiation, in children <10 years of age, while using a filtered back projection reconstruction algorithm. Image quality of 119 pediatric head CTs was assessed using a 5-point scoring system. Exams with scores ≥2.5 were considered of sufficient diagnostic quality. The contrast-to-noise ratio (CNR) was also measured. For children <1 year and 1-9 years, all studies performed with CTDIvol ≥ 20.1 mGy (range: 9-46 mGy) and CTDIvol ≥ 27.5 mGy (range: 15-60 mGy) yielded images of diagnostic quality. All diagnostic studies had a minimum CNR of 1.4. These CTDIvol values represent a good balance between image quality and radiation burden. This information can be helpful in designing pediatric head CT protocols with further dose-reduction, namely, iterative reconstruction algorithms and automated exposure control.