Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series.

BACKGROUND AND PURPOSE: Epileptic seizures account for 24-40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs). METHODS: We retrospectively reviewed the angioarchitectural features of AVMs associated with seizures in 168 patients admitted to our Department from 1997 to 2012. Patients were dichotomized according to demographic characteristics, type of treatment, bleeding occurrence, and morphological and topographic features. Clinical status at admission and discharge was also recorded. The association of each one of these variables with seizures occurrence was statistically tested. Continuous variables and outcome were compared with Student's t-test, whereas categorical ones were compared using Fisher's exact test. The independent contribution of some seizures predictors was assessed with a logistic regression model. Associations were considered significant for P < 0.05. RESULTS: About 29% patients showed seizures and 47% bleeding. No significant difference in age and sex was observed between patients with and without seizures. AVMs > 4 cm (P = 0.001) and those fed by dilated arterial feeders (P = 0.02) were associated with increased risk of seizures. A higher risk of seizures occurrence was also observed in cortical AVMs compared with deeper ones (75.5% vs. 55.4%; P = 0.01), and in AVMs fed by middle and posterior cerebral arteries branches compared with the other vessels (81.6% vs. 45.3%; P < 0.001 and 48.9% vs. 23.5%; P = 0.002, respectively). No lobar predisposition was observed. A nidus > 4 cm also appeared as an independent risk factor of seizures occurrence (OR 2.82; 95% CI, 1.26-6.31; P = 0.009) at logistic regression analysis. CONCLUSIONS: AVM morphology, especially nidus dimension, appeared to more significantly influence seizures occurrence than their topography.

Autosomal recessive limb-girdle muscular dystrophy, LGMD2F, is caused by a mutation in the delta-sarcoglycan gene.

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of inherited neuromuscular disorders characterized by proximal muscular weakness of the pelvic and shoulder girdles and a variable progression with symptoms, ranging from very severe to mild. One autosomal dominant (LGMD1A, at chromosome 5q22.3-31.3) (ref. 3) and five autosomal recessive (AR) loci responsible for this phenotype have been identified: LGMD2A at 15q (ref. 4); LGMD2B at 2p (ref. 5), LGMD2C at 13q (ref. 6), LGMD2D at 17q (ref. 7) and LGMD2E at 4q (refs 8,9). In the muscle membrane, dystrophin associates with several proteins and glycoproteins organized in two main subcomplexes: the dystroglycan (DG) and sarcoglycan (SG) complexes. The genes for LGMD2C, LGMD2D and LGMD2E code for proteins of the SG complex. We recently mapped a sixth AR form of LGMD, LGMD2F, to chromosome 5q33-34 in two Brazilian families. In the same chromosomal interval we also mapped the delta SG gene, encoding a novel 35-kD component of the sarcoglycan (SG) complex. We now show that a homozygous mutation in the delta SG gene (a single nucleotide deletion that alters its reading frame) is the cause of LGMD2F.

Nanotechnology and vascular neurosurgery: an in vivo experimental study on microvessels repair using laser photoactivation of a nanostructured hyaluronan solder.

Sealing tissues by laser in neurosurgical procedures may overcome problems related to the use of conventional suturing methods which can be associated with various degrees of vascular wall damage. Despite the significant experimental and clinical achievements of the past, a standardized clinical application of laser-welding technology has not yet been implemented. The main problem is related to the use of common organic chromophores. A substantial breakthrough in the laser welding of biological tissues may come from the advent of nanotechnologies. In this paper we describe an experimental study, to confirm the feasibility of an innovative laser-assisted vascular repair (LAVR) technique based on diode laser irradiation and subsequent photoactivation of a hyaluronan solder embedded with near infrared (NIR) absorbing gold nanorods (GNRs), and to analyze the induced closuring effect in a follow-up study performed in animal model. Twenty New Zealand rabbits underwent closure of a 3-mm longitudinal incision performed on the common carotid artery (CCA) by means of 810 nm diode laser irradiation, in conjunction with the topical application of an optimized GNR composite. Effective closure of the arterial wound was accomplished by using very low laser intensity (30 W/cm2). The average CCA occlusion time was as low as 50 sec. Animals underwent different follow-up periods (2, 8, 30 days). After follow-up, they were re-anesthetized, the patency of the treated vessels was tested (Doppler analysis) and then the irradiated vessels were excised and subjected to histological evaluations. Morphological examinations of the samples documented the integrity of the vascular wall. No host reaction to nanoparticles occurred. Collagen and elastic fibers returned to their normal architecture 30 days after treatment. A Scanning Electron Microscopy (SEM) examination and immuno-histochemical analysis demonstrated a full re-endothelization of the vessel walls. We thus confirmed that a laser-based approach is technically easy to perform, and provides several advantages, such as a simplification of the surgical procedure, a reduction in the operative time, and the suppression of bleeding. The use of GNRs improves the selectivity of welding and minimizes the surgical trauma to vessels, resulting in an optimal healing process.

Present status and new perspectives in laser welding of vascular tissues.

The laser welding of biological tissues is a particular use of lasers in surgery. The technique has been proposed since the 1970s for surgical applications, such as repairing blood vessels, nerves, tendons, bronchial fistulae, skin and ocular tissues. In vascular surgery, two procedures have been tested and optimized in animal models, both ex vivo and in vivo, in order to design different approaches for blood vessels anastomoses and for the repair of vascular lesions: the laser-assisted vascular anastomosis (LAVA) and the laser-assisted vessel repair (LAVR). Sealing tissues by laser may overcome the problems related to the use of conventional closuring methods that are generally associated with various degrees of vascular wall damage that can ultimately predispose to vessel thrombosis and occlusion. In fact, the use of a laser welding technique provides several advantages such as simplification of the surgical procedure, reduction of the operative time, suppression of bleeding, and may guarantee an optimal healing process of vascular structures, very similar to restitutio ad integrum. Despite the numerous preclinical studies performed by several research groups, the clinical applications of laser-assisted anastomosis or vessel repair are still far off. Substantial breakthrough in the laser welding of biological tissues may come from the advent of nanotechnologies. Herein we describe the present status and the future perspectives in laser welding of vascular structures.

An experimental study on minimally occlusive laser-assisted vascular anastomosis in bypass surgery: the importance of temperature monitoring during laser welding procedures.

Laser welding has been proposed as an alternative technique to conventional stitching in microvascular anastomosis, with the advantages of improving the vascular healing process and reducing the risk of malfunction of a bypass. Our group recently proposed a laser-assisted end-to-side anastomotic technique, providing the advantages of laser welding and reducing the occlusion time of the recipient vessel, that is important in neurosurgical bypass procedures, in order to reduce the risk of cerebral ischemia. This in vivo study focuses on the control of the temperature dynamics developing in the welded tissue. A jugular vein graft was harvested and implanted on the rabbit carotid artery by means of two end-to-side anastomosis. Laser welding procedure was then carried out to implant the bypass. A real-time monitoring of the temperature during welding was performed with an infrared thermocamera, in order to control the laser-induced heating effect on the external surface of the vessel walls. The temperature analysis highlighted the dynamic of the heating effect in space and time and enabled us to define an optimal temperature range in operative conditions. The temperature control provided safe tissue heating confined within the directly irradiated area, with negligible damage to surrounding tissues, as well as effective sealing and welding of the vessel edges at the anastomotic sites. The average occlusion time of the carotid artery was about 11 minutes. After a follow-up of 30 days, all the bypasses were patent and no signs of thrombosis or leak point pressure were present, thus confirming the safety of this laser-assisted anastomotic procedure.

A bioavailability study on microbeads and nanoliposomes fabricated by dense carbon dioxide technologies using human-primary monocytes and flow cytometry assay.

Supercritical Emulsion Extraction (SEE) and Supercritical assisted Liposome formation (SuperLip), use dense gases such as carbon dioxide (dCO2) to fabricate advanced micro/nanocarriers. SEE uses dCO2 to extract solvent from the oily phase of an emulsion and obtain biopolymer microbead; For this study, poly-Lactic Acid (PLA) microbeads of 1 ±â€¯0.2 µm in mean size loaded at 1 µg/mgPLA with Rhodamine B (ROD) were prepared by SEE; the beads showed a solvent residue lower than 10 ppm and encapsulated the fluorochrome with an efficiency of 90%. SuperLip uses dCO2 to enhance lipid/ethanol/water mixing and to promote the ethanol extraction from liposome suspension. In this case, phosphatidyl-choline (PC) vesicles with a mean size of 0.2 ±â€¯0.05 µm and loaded with Fluorescein Iso-ThioCyanate (FITC) at 8 µg/mgPC were prepared; small unilamellar structure was observed for all the vesicles with FITC encapsulation efficiency of 80%. Ethanol residue of 50 ppm was measured in all the liposome suspensions. The bioavailability of microbeads and nanoliposomes was assessed through incubation with human monocytes previously isolated from healthy donors' blood. A specifically optimized protocol that allowed their quenching on the cell surface was developed to monitor by flow cytometer assay only the cell population that effectively internalized the carriers. When microbeads were tested, the percentage of alive internalizing monocytes was of about 30%. An internalization of 96.1 ±â€¯21% was, instead, obtained at dosage of 0.1 mg/mL for nanoliposomes. In this last case, monocytes showed a vitality of almost 100% after vesicles internalization at all the concentrations studied; on the other hand, cell apoptosis progressively increased in a dose/response manner, after polymer microbeads phagocytosis. The proposed data suggested that dCO2 technologies can be reliably used to fabricate intracellular carriers.

Middle cerebral artery dolichoectasia in a young woman with a previous stroke.

We observed a 32-year-old female who had suffered from a left hemisphere ischemic stroke with right hemiparesis at the age of seven. At that time, a CT scan demonstrated a left ischemic lesion in nucleo-capsular region and a cerebral angiogram documented a complete occlusion of the supraclinoid segment of the internal carotid artery. When we observed the patient neurological examination demonstrated a moderate right brachio-crural hemiparesis. A brain MRI showed an old ischemic lesion involving the left nucleo-capsular and 'flow voids' suggestive for a vascular malformation in the left sylvian region. A cerebral rotational angiogram with 3-D reconstructions demonstrated a dolichoectatic left middle cerebral artery with an unusual 'corkscrew' aspect. Middle cerebral artery dolichoectasia is a rare pathological condition that may manifest with a stroke. The patients with intracranial arterial dolichoectasia (IADE) are most often hypertensive elderly men, and, to the best of our knowledge, an ischemic stroke associated with IADE has never been reported in children.

Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington's disease transgenic R6/2 (160 CAG) mice.

Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found.

Diagnosis and management of dural arteriovenous fistulas: a 10 years single-center experience.

OBJECTIVES: Dural arteriovenous fistulas (DAVFs) are a challenging condition in vascular neurosurgery. Disease natural history and its management is still debated. In the present paper we report our center series on DAVFs over a period of 10 years. Our data were compared with relevant literature. PATIENT AND METHODS: Our series includes 45 cases: 14 cavernous sinus, 11 transverse-sigmoid, 8 patients tentorial, 6 anterior cranial fossa, 5 patients spinal, 1 patient foramen magnum. RESULTS AND CONCLUSIONS: DVAFs distribution, clinical presentation and hemorrhagic risk are discussed. Cavernous sinus DAVFs are the most common site in our series. Other locations in order of frequency are transverse-sigmoid sinus, tentorial, anterior cranial fossa, spinal and foramen magnum. The majority of patients presented with non-aggressive symptoms. 18% presented with intracranial hemorrhage: all the hemorrhages occurred in high-grade DAVFs. For most patients, endovascular treatment, transarterial or transvenous, was the first option. Surgery was performed for the anterior cranial fossa DAVFs and other complex lesions draining mostly transverse-sigmoid sinus and tentorium. In 7% of cases a combination of endovascular+surgical treatment was used. Our series has been carefully analyzed in comparison 'side by side' with most relevant literature on DVAFs, focusing particularly on management strategies, therapeutic options and risks related to treatment.

Reinitiation of protein synthesis in Escherichia coli can be induced by mRNA cis-elements unrelated to canonical translation initiation signals.

In Eubacteria, de novo translation of some internal cistrons may be inefficient or impossible unless the 5' neighboring cistron is also translated (translational coupling). Translation reinitiation is an extreme case of translational coupling in which translation of a message depends entirely on the presence of a nearby terminating ribosome. In this work, the characteristics of mRNA cis-elements inducing the reinitiation process in Escherichia coli have been investigated using a combinatorial approach. A number of novel translational reinitiation sequences (TRSs) were thus identified, which show a wide range of reinitiation activities fully dependent on a translational coupling event and unrelated to the presence/absence of secondary structure or mRNA stability. Moreover, some of the isolated TRSs are similar to intercistronic sequences present in the E. coli genome.

Identification and characterization of a novel member of the dystrobrevin gene family.

A new member of the dystrobrevin gene family was identified using a bioinformatics approach. Sequence analysis indicates that this gene, named DTN-B, is highly homologous to the rabbit A0, the previously described dystrobrevin (DTN), Torpedo 87 kDa and to the C-terminus of dystrophin. The coiled-coil domain, shown to be the site of interaction between dystrobrevins and dystrophin, is highly conserved. Immunostaining studies indicate that DTN-B and DTN expression is absent in affected muscle fibers from DMD patients and carriers.

Lack of sodium channel mutation in an Italian family with paramyotonia congenita.

OBJECTIVE: To conduct the genotype-phenotype correlation in a family in which several individuals share clinical and electrophysiologic features of paramyotonia congenita (PC). BACKGROUND: PC, hyperkalemic periodic paralysis (HyperPP), and potassium-aggravated myotonias form the group of hereditary sodium channelopathies. Each of these disorders is associated with different point mutations in SCN4A, the gene encoding the alpha-subunit of the adult human skeletal muscle sodium channel. However, in HyperPP families, evidence of a causative gene different from SCN4A has been found. METHODS: We conducted direct clinical examination, electrophysiologic (EMG/electroneurographic) and cardiologic studies, as well as laboratory screening in several affected and nonaffected members of the family. We performed the genotype-phenotype correlation by microsatellite linkage and cDNA-mutation analyses of the SCN4A gene. RESULTS: Affected members in this family showed clinical and electrophysiologic features typical of PC. The disease phenotype segregated with the chromosomal region that includes the SCN4A gene. Analysis of the entire cDNA sequence of the SCN4A gene in the index case disclosed a G3826A transition, which results in the Val1276Ile substitution. However, PCR-single-stranded confirmation polymorphism and direct sequencing analysis of the segment coding for Val-1276 on genomic DNA confirmed the G3826A transition in the index case but was negative in 11 affected members of the family; however, neither mutations nor aberrant splicings causative of the PC phenotype in this family were found on SCN4A. CONCLUSION: The existence of a second gene different from SCN4A that can give rise to a clinical PC phenotype can be speculated upon.

A novel p53 mutant in human breast cancer revealed by multiple SSCP analysis.

DNA from tumor tissue and peripheral blood lymphocytes of primary breast cancer patients was screened for the presence of p53 mutations. In DNA from one tumor we found that the histidine codon 193 (CAT) was somatically converted to arginine (CGT). This amino acid residue is highly conserved in many species, thus suggesting that such mutation plays an important role in the loss of wt-p53 function.

Exceptional familial clustering for extreme longevity in humans.

Four families highly clustered for extreme longevity are described here, representing the first report of clustering for this phenotype. Families such as these may prove to be helpful in the further understanding of the genetic contribution to achieving exceptional longevity.

Genomic organization and single-nucleotide polymorphism map of desmuslin, a novel intermediate filament protein on chromosome 15q26.3.

BACKGROUND: Desmuslin is an alpha-dystrobrevin-interacting protein expressed primarily in heart and skeletal muscle. The desmuslin protein interacts with and is closely related to desmin, a protein encoded by a locus mutated in some forms of hereditary distal myopathy. As a muscle-specific intermediate filament protein, desmuslin is also a candidate for myopathies of unknown etiology. RESULTS: The desmuslin gene was localized to chromosome 15q26.3 by electronic screening of the human DNA sequence database. Primer pairs were designed to amplify the 5 exons of the desmuslin gene in 11 overlapping DNA segments. The desmuslin gene was screened for mutations in 71 patients with various forms of myopathy for which there was no known cause. In this analysis, 10 common and 2 rare amino acid altering single-nucleotide polymorphisms were identified, all of which were seen in a control population of individuals thus making these unlikely causes of the phenotype. Interestingly, one of the single-nucleotide polymorphisms found in a patient resulted in a premature stop codon in the first exon. The nonsense mutation was also detected in the patient's unaffected father and one unaffected control; it was detected in 0.44% (2/454) of unrelated chromosomes and is therefore predicted to have a homozygous frequency of 0.002%. CONCLUSION: No causative mutations were found in the desmuslin gene. However, the single-nucleotide polymorphisms mapped in this study represent a well-mapped group that can be used for disequilibrium studies of this region of chromosome 15q26.3.

Cerebrospinal fluid shunting for hydrocephalus in the adult: factors related to shunt revision.

Cerebrospinal fluid shunting procedures are widely employed in the treatment of hydrocephalus and other disturbances of the dynamics of cerebrospinal fluid. In spite of its popularity, this operation frequently requires surgical revision. A retrospective analysis of a series of 356 adults who underwent the insertion of a cerebrospinal fluid shunt between January 1970 and December 1988 was performed. The incidence of revision was analyzed, and an attempt was made to identify possible causal factors. The overall incidence of surgical revisions was 28.65%; the number of revisions in the same patient ranged between one and eight. The most frequent causes of revision were distal malposition, obstruction, and infection. A statistically significant difference (P less than 0.05) was found in both the risk of revision in patients who had undergone previous operations and those who had not and in the incidence of revision before and after January 1985. Meticulous surgical technique as well as perioperative antibiotic prophylaxis appear responsible for the latter. The differences in the incidence of revision among patients treated with different types of shunts and valves, though remarkable, is not statistically significant.

Intracranial epithelioid hemangioendothelioma: case report.

We report the case of a 27-year-old man who underwent surgical excision of an intracranial extra-axial right temporal lesion. A preoperative embolization with the use of a mixture of N-butyl-cyanoacrylate, ultrafluid-lipiodol, and micronized tungsten was necessary to devascularize the tumor. The histological diagnosis was epithelioid hemangioendothelioma. The patient was neurologically intact and tumor-free 18 months after surgery. To our knowledge, this is the fifth patient reported with intracranial epithelioid hemangioendothelioma and the first adult patient for whom complete data are available.

Multiple intracranial metastases of malignant melanoma with long-term survival. Case report.

The authors present a case of multiple brain metastases and an extracranial secondary localization from malignant melanoma. The patient was operated on three times for the intracranial masses and had a 49-month survival with a good quality of life after the first of the three operations. She lived a total of 80 months from the time of diffusion of the primary tumor. The course of malignant melanoma is unpredictable, and long-term survival can be achieved in some cases, even in the presence of multiple brain metastases.