VEGF protects brain against focal ischemia without increasing blood--brain permeability when administered intracerebroventricularly.

Delayed administration of vascular endothelial growth factor (VEGF) promotes functional recovery after focal cerebral ischemia. However, early intravenous injection of VEGF increases blood-brain barrier (BBB) leakage, hemorrhagic transformation and infarct volume whereas its application to cortical surface is neuroprotective. We have investigated whether or not early intracerebroventricular administration of VEGF could replicate the neuroprotective effect observed with topical application and the mechanism of action of this protection. Mice were subjected to 90 mins middle cerebral artery (MCA) occlusion and 24 h of reperfusion. Vascular endothelial growth factor (8 ng, intracerebroventricular) was administered 1 or 3 h after reperfusion. Compared with the vehicle-treated (intracerebroventricular) group, VEGF decreased the infarct volume along with BBB leakage in both treatment groups. Neurologic disability scores improved in parallel to the changes in infarct volume. Independently of the decrease in infarct size, VEGF also reduced the number of TUNEL-positive apoptotic neurons. Phospo-Akt levels were significantly higher in ischemic hemispheres of the VEGF-treated mice. Contrary to intracerebroventricular route, intravenous administration of VEGF (15 microg/kg) enhanced the infarct volume as previously reported for the rat. In conclusion, single intracerebroventricular injection of VEGF protects brain against ischemia without adversely affecting BBB permeability, and has a relatively long therapeutic time window. This early neuroprotective action, observed well before recovery-promoting actions such as angiogenesis, possibly involves activation of the PI-3-Akt pathway.     

Stroke and status epilepticus: stroke type, type of status epilepticus, and prognosis.

Even though stroke is known to be a common cause of status epilepticus (SE), the types of stroke or SE that may be associated are not yet clearly defined. The aims of this study were to assess the timing and type of SE in stroke patients and to observe the effects of stroke and the type of SE on the response to treatment and mortality.From May 1998 to May 2001 a total of 121 patients were admitted with SE. Among these, 30 cases (24.8%) of poststroke SE were identified and evaluated. There were 20 early-onset, and 10 late-onset SE. All stroke types were evenly distributed within the early-onset group, whereas only ischaemic stroke was found in the late-onset group. Posterior cerebral artery (PCA) infarcts were significantly more common within the latter (P: 0.0017). Nonconvulsive SE (NCS) was more frequent than convulsive SE (CS) in the early-onset group (P: 0.0352). There was a delay in the time-to-treatment for NCS compared to CS (P: 0.0007). Without, however any effect on the rate of response to first step treatment (intravenous diazepam and phenytoin; P: 0.6334). Thirteen patients died (43.3%) during hospitalisation. Disability was significantly associated with higher mortality in the early-onset group (P: 0.0201). As a conclusion, NCS seems to be an important issue in stroke, thus requiring a high degree of suspicion in an acute stroke setting to avoid further neuronal injury and morbidity.     

The efficacy of hyperbaric oxygen for the treatment of experimental uveitis induced in rabbits

OBJECTIVE: The aim of the present study was to examine the efficacy of hyperbaric oxygen (HBO) therapy in the treatment of experimental uveitis induced in rabbits. It was hypothesized that HBO therapy improves the regression of experimental uveitis induced in rabbits. RESEARCH DESIGN AND METHODS: An experimental animal study was conducted on 48 rabbits (48 right eyes of these rabbits) to evaluate the effects of HBO therapy on endotoxin-induced acute anterior uveitis in rabbits. To induce acute anterior uveitis, Salmonella typhimurium lipopolysaccharide endotoxin (LPS) was intravitreally injected into the right eyes of the rabbits. The animals were randomly assigned to five groups. No treatment was given to the rabbits in Group A. Prednisolone acetate was topically administered to the rabbits in Group B. Methylprednisolone acetate was administered by anterior subtenon injection to the rabbits in Group C four hours after LPS application. HBO therapy was administered to the rabbits in Group D. Both HBO therapy and anterior subtenon injection of methylprednisolone therapy were administered to the rabbits in Group E. To compare the effects of the different therapies on the progression of endotoxin-induced uveitis, examinations including clinical scoring of anterior uveitis, microscopic examination of aspirated aqueous humor for inflammatory responses, and aqueous protein level assessment were performed once a day after LPS injection. RESULTS: There was a statistically significant difference between the control group (Group A) and other groups (Groups B-E) with respect to the number of inflammatory cells and protein levels in the aqueous one and three days after LPS injection (p < 0.05), indicating that the treatments resulted in less inflammation in Groups B-E compared to Group A. Moreover, there was no statistically significant difference between Groups B and C, Groups B and D, Groups B and E, Groups C and D, and Groups C and E with regard to the number of inflammatory cells in the aqueous at Day 1 after LPS injection (p > 0.05). In addition, Groups B and C and Groups B and D were comparable with regard to cell counts at Day 3 (p > 0.05), showing that HBO was comparable to corticosteroids in reducing inflammation. The differences between Groups B and E and Groups C and E were significant with regard to aqueous cell counts at Day 3 (p < 0.05), showing that HBO plus steroid was more effective than steroids alone. CONCLUSION: The intensity of ocular inflammation in the group receiving HBO therapy combined with anterior subtenon injection of methylprednisolone therapy was lower than in the other groups. We also demonstrated that HBO therapy was an effective therapeutic modality for the treatment of experimental uveitis induced in rabbits with an efficacy comparable to that of corticosteroids. Moreover, HBO plus steroid was superior to steroids alone in reducing inflammation.     

Myocardial infarction and arterial thrombosis in identical newborn twins with homozygosity for the PAI-1 4 G/5 G polymorphism

Myocardial infarction in the perinatal period, in the absence of congenital heart disease or coronary artery lesions, is rare. The most common etiology described are the thromboembolism and perinatal asphyxia. We report a case of monozygotic twins who developed, after birth, acute vascular events and both had PAI-1 4G/4G homozygosity.     

Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an <Emphasis Type="Italic">ALS2</Emphasis> founder variant

Biallelic mutations of the alsin Rho guanine nucleotide exchange factor (ALS2) gene cause a group of overlapping autosomal recessive neurodegenerative disorders including infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (JALS/ALS2), caused by retrograde degeneration of the upper motor neurons of the pyramidal tracts. Here, we describe 11 individuals with IAHSP, aged 2–48 years, with IAHSP from three unrelated consanguineous Iranian families carrying the homozygous c.1640+1G>A founder mutation in ALS2. Three affected siblings from one family exhibit generalized dystonia which has not been previously described in families with IAHSP and has only been reported in three unrelated consanguineous families with JALS/ALS2. We report the oldest individuals with IAHSP to date and provide evidence that these patients survive well into their late 40s with preserved cognition and normal eye movements. Our study delineates the phenotypic spectrum of IAHSP and ALS2-related disorders and provides valuable insights into the natural disease course.     

Serial EEG and MRI changes in status epilepticus-induced excitotoxic neuronal necrosis

Prolonged status epilepticus may directly cause selective neuronal necrosis due to excitotoxic mechanisms, as observed in experimental models and described in case reports. A 36-year-old woman presented with right hemiplegia and aphasia following a generalised tonic-clonic status epilepticus of two hours duration. Accompanying serial MRI with advanced imaging techniques, EEG and histopathology of the cortical tissue of the patient were all compatible with excitotoxic neuronal necrosis. In this histopathologically-proven rare case of status epilepticus-induced excitotoxic neuronal injury, the observation of delayed cortical laminar necrosis on MRI, together with paroxysmal lateralised epileptiform discharges on the EEG, suggests that these changes may be an early sign of impending and ongoing excitotoxic neuronal injury and delayed cell death caused by glutamate release due to excessive neuronal firing in status epilepticus.     

Selective laser trabeculoplasty induced changes in the thickness of ciliary body and iris evaluated by ultrasound biomicroscopy

Background

Selective laser trabeculoplasty (SLT) is widely used for the treatment of glaucoma. The main target tissue of this treatment modality is trabecular meshwork. We aimed to detect the SLT-induced changes in the thickness of ciliary body (CBT) and iris (IT), quantitatively.

Methods

Thirty-one patients treated by SLT were examined by ultrasound biomicroscopy (UBM) at different locations of ciliary body and iris at four quadrants, before and after (3rd, 7th, and 30th days) SLT. The IT was measured at various locations; 500???m anterior to the scleral spur (IT₁), 2?mm from the iris root (IT₂) and near the pupillary edge where the iris thickness was maximum (IT₃) at four quadrants. The CBT at positions 1 and 2?mm posterior to the scleral spur were measured (CBT_1-2). Additionally, intraocular pressure (IOP) levels were measured in all visits and post-laser 1 h.

Results

There were statistically significant higher CBT values at 3rd and 7th-day measurements in the study compared to pre-treatment levels (p?<?0.0001, p?<?0.0001, respectively). CBT₂ values at day 30 were similar compared to pre-treatment values (overall p?=?0.140), but CBT₁ values at day 30 were not exactly similar compared to pre-treatment values in superior and nasal quadrants (overall p?=?0.027). IT values obtained in the 3rd and 7th days were significantly higher in all quadrants and regions when compared to the pre-treatment values (p?<?0.0001, p?<?0.0001, respectively). There were no statistically significant differences in any of the IT values at the 30th day in comparison to the pre-treatment values (p?=?0.45).

Conclusions

The results suggest that SLT induces prominent increases in CBT and IT returning to baseline thickness in a month, which may be caused by inflammation, vascular engorgement, or mechanical muscular contraction.