Arterial spin labeling perfusion MRI at multiple delay times: a correlative study with H215O positron emission tomography in patients with symptomatic carotid artery occlusion

Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) with image acquisition at multiple inversion times is a noninvasive ASL technique able to compensate for spatial heterogeneities in transit times caused by collateral blood flow in patients with severe stenosis of the cerebropetal blood vessels. Our aim was to compare ASL-MRI and H₂¹⁵O positron emission tomography (PET), the gold standard for cerebral blood flow (CBF) assessment, in patients with a symptomatic internal carotid artery (ICA) occlusion. Fourteen patients (63±14 years) with a symptomatic ICA occlusion underwent both ASL-MRI and H₂¹⁵O PET. The ASL-MRI was performed using a pulsed STAR labeling technique at multiple inversion times within 7 days of the PET. The CBF was measured in the gray-matter of the anterior, middle and posterior cerebral artery, and white-matter. Both PET and ASL-MRI showed a significantly decreased CBF in the gray-matter of the middle cerebral artery in the hemisphere ipsilateral to the ICA occlusion. The average gray-matter CBF measured with ASL-MRI (71.8±4.3 mL/min/100 g) was higher (P<0.01) than measured with H₂¹⁵O PET (43.1±1.0 mL/min/100 g). In conclusion, ASL-MRI at multiple TIs is capable of depicting areas of regions with low CBF in patients with an occlusion of the ICA, although a systematic overestimation of CBF relative to H₂¹⁵O PET was noted.     

Mechanisms of primary blast-induced traumatic brain injury: insights from shock-wave research

Traumatic brain injury caused by explosive or blast events is traditionally divided into four phases: primary, secondary, tertiary, and quaternary blast injury. These phases of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury phase represents the response of brain tissue to the initial blast wave. Among the four phases of bTBI, there is a remarkable paucity of information about the cause of primary bTBI. On the other hand, 30 years of research on the medical application of shockwaves (SW) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by supersonic flow. The resultant tissue injury includes several features observed in bTBI, such as hemorrhage, edema, pseudoaneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation, are all important factors in determining the extent of SW-induced tissue and cellular injury. Herein we describe the requirements for the adequate experimental set-up when investigating blast-induced tissue and cellular injury; review SW physics, research, and the importance of engineering validation (visualization/pressure measurement/numerical simulation); and, based upon our findings of SW-induced injury, discuss the potential underlying mechanisms of primary bTBI.     

Macrocephaly-capillary malformation: Analysis of 13 patients and review of the diagnostic criteria

Macrocephaly-capillary malformation (M-CM) is a genetic syndrome of unknown etiology characterized by an enlarged head circumference and patchy, reticular capillary malformation. We describe the clinical features of 13 cases, report on the genome-wide Copy Number Variation characterization of these patients, analyze the main clinical features of this syndrome and propose a modification of the current diagnostic criteria: the inclusion of both overgrowth/asymmetry and neuroimaging alterations as major criteria.     

Intraneural hematoma with extrinsic compression: experimental study in rats and therapeutic options

Intraneural hematoma can result in the median nerve in the carpal tunnel after trauma or coagulation disorders. The decision for expectant management or decompressive surgical techniques is still controversial. Fifty male Wistar rats were divided into five groups. The sciatic nerve was wrapped around with a silastic device in four groups. In group A, the sciatic nerve was just wrapped by the silastic tube. In group B, an intraneural injection of autologous blood was added. In group C, after the hematoma creation, the silastic device was removed and a longitudinal epineurotomy was performed. In group D, the silastic device was removed after the hematoma, but the nerve was not opened. In group E (sham-operated), the sciatic nerve was exposed without hematoma or compression. Nerve function recovery was assessed periodically over 61 days using the Bain-Mackinnon-Hunter Sciatic Function Index (SFI). Group A (extrinsic compression) presented initial SFI of -26.29 +/- 2.89, with return to baseline values on the fifth postoperative day. Group B (hematoma and extrinsic compression) exhibited the poorest function (SFI of -85.23 +/- 3.51) after surgery and recovery in 23 days. Group C (liberation of silastic and hematoma drainage through epineurotomy) and group D (only removal of the silastic tube) presented similar initial SFI values of -32.78 +/- 7.45 and -45.13 +/- 6.84, respectively. In both the groups, the SFI values returned to baseline level on fifth postoperative day. The statistical analysis of SFI identified a significant difference (P < .0001) between the expectant management (group B) and the descompressive surgery approach (groups C and D) by 1st to 19th postoperative day. The number of degenerative fibers and density of degenerative fibers were statistically significantly longer in group B when compared with the other groups. There was no statistical difference between the other groups when these parameters were analyzed. Thus, immediate decompressive procedures of the intraneural hematoma provide a faster functional recovery and reduce the damage to the axon fibers.     

Selective inhibition of early--but not late--expressed HIF-1α is neuroprotective in rats after focal ischemic brain damage

The expression of hypoxia-inducible factor-1-alpha (HIF-1α) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF-1α was observed during 1-12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2-methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre-silencing HIF-1α with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip-like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF-1α with siRNA 12 h after oxygen-glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate that HIF-1α induced by ischemia in early and late times leads cellular apoptosis and survival, respectively, and provides a new insight into the divergent roles of HIF-1α expression in neurons after ischemic stroke.     

Beckwith-Wiedemann syndrome and uniparental disomy 11p: fine mapping of the recombination breakpoints and evaluation of several techniques

Beckwith-Wiedemann syndrome (BWS) is a phenotypically and genotypically heterogeneous overgrowth syndrome characterized by somatic overgrowth, macroglossia and abdominal wall defects. Other usual findings are hemihyperplasia, embryonal tumours, adrenocortical cytomegaly, ear anomalies, visceromegaly, renal abnormalities, neonatal hypoglycaemia, cleft palate, polydactyly and a positive family history. BWS is a complex, multigenic disorder associated, in up to 90% of patients, with alteration in the expression or function of one or more genes in the 11p15.5 imprinted gene cluster. There are several molecular anomalies associated with BWS and the large proportion of cases, about 85%, is sporadic and karyotypically normal. One of the major categories of BWS molecular alteration (10-20% of cases) is represented by mosaic paternal uniparental disomy (pUPD), namely patients with two paternally derived copies of chromosome 11p15 and no maternal contribution for that. In these patients, in addition to the effects of IGF2 overexpression, a decreased level of the maternally expressed gene CDKN1C may contribute to the BWS phenotype. In this paper, we reviewed a series of nine patients with BWS because of pUPD using several methods with the aim to evaluate the percentage of mosaicism, the methylation status at both loci, the extension of the pUPD at the short arm and the breakpoints of recombination. Fine mapping of mitotic recombination breakpoints by single-nucleotide polymorphism-array in individuals with UPD and fine estimation of epigenetic defects will provide a basis for understanding the aetiology of BWS, allowing more accurate prognostic predictions and facilitating management and surveillance of individuals with this disorder.     

Exploring the association between cardiovascular and other disease‐related risk factors in the psoriasis population: the need for increased understanding across the medical community

There is abundant and accumulating evidence on the classification of psoriasis as a systemic disease that exhibits a host of co‐morbidities. As a consequence, the second Interdisciplinary Conference on Co‐morbidities and Lifestyle Modification, convened by the International Psoriasis Council, has concluded that specialist physicians, primary care physicians and dermatologists are faced with an opportunity to impact, not just psoriasis disease understanding and management, but overall patient well‐being. The conference panel was represented by the disciplines of dermatology, cardiology, rheumatology, epidemiology, endocrinology, hepatology and gastroenterology, and medical specialists with particular expertise in obesity, diabetes mellitus, inflammation and genetics. The multiple co‐morbidities associated with psoriasis were reviewed with a view to identify possible mechanisms linking psoriatic disease with obesity, metabolic syndrome, diabetes, cardiovascular disease and non‐alcoholic fatty liver disease. Consensus was established on the association of psoriasis with other co‐morbidities and disease states. Consequently, there is a significant opportunity for specialist and primary care physicians to collaborate with dermatologists in the management of the overall health of psoriasis patients. First, there is an important need for physicians to routinely screen psoriasis patients for the multiple susceptibility risk factors and co‐morbidities associated with psoriasis. Second, the design and implementation of lifestyle modification plans including exercise, diet and the limitation of alcohol and tobacco intake, will not only benefit their general medical health but also their psoriasis.