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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 μg/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.

Methylenetetrahydrofolate reductase gene polymorphisms are associated with ischemic and hemorrhagic stroke: Dual effect of MTHFR polymorphisms C677T and A1298C.

Hyperhomocysteinemia is an independent risk factor for ischemic stroke. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a critical role in modulating the levels of plasma homocysteine. Two polymorphisms in the MTHFR gene, C677T, A1298C result in reduced enzyme activity. The mechanisms of ischemic and hemorrhagic stroke are not well understood. Although controversial, previous studies have shown evidence of causality of both stroke subtypes in patients with methylenetetrahydrofolate reductase gene polymorphisms. Therefore, we examined whether the C677T and A1298C polymorphisms of MTHFR gene are genetic risk factors for both ischemic and hemorrhagic stroke in a Turkish Caucasian population. In a case-control study, 120 total unrelated stroke patients (92 ischemic stroke, 28 hemorrhagic stroke), and 259 healthy controls were genotyped for C677T and A1298C polymorphisms of the MTHFR gene using a PCR-RFLP based-method. The MTHFR 1298C allele (chi(2)=8.589; P=0.014), C1298C genotype (OR=2.544; P=0.004), and C677C/C1298C compound genotype (OR=3.020; P=0.001) were associated with overall stroke. The MTHFR 1298C allele (chi(2)=11.166; P=0.004), C1298C genotype (OR=2.950; P=0.001), and C677C/C1298C compound genotype (OR=3.463, P=0.0001) were strongly associated with ischemic stroke. Interestingly however, the MTHFR 677T allele (chi(2)=6.033; P=0.049), T677T genotype (OR=3.120; P=0.014), and T677T/A1298A compound genotype (OR=4.211; P=0.002) were associated with hemorrhagic stroke. In conclusion, the C677T and A1298C polymorphisms of the MTHFR gene are genetic risk factors for hamorrhagic and ischemic stroke respectively, independent of other atherothrombotic risk factors.

The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: A randomized, double-blind, placebo-controlled, multicenter study

Cognitive impairment can occur at all stages of Parkinsons disease. Rasagiline is a selective monoamine oxidase type‐B inhibitor that enhances central dopaminergic transmission. Dopamine is thought to be involved in certain cognitive processes such as working memory. We assessed the effects of rasagiline on cognitive deficits in cognitively impaired, nondemented patients with Parkinsons disease. This was a randomized, double‐blind, placebo‐controlled prospective study. Patients with Parkinsons disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months. Patients were eligible if they had impairment in 2 of 4 cognitive domains (attention, executive functions, memory, visuospatial functions) in the screening neuropsychological tests, yet did not fulfill criteria for Parkinsons disease dementia. Fifty‐five patients were randomized; 48 patients completed the study. Patients in the rasagiline group showed significant improvement in digit span–backward compared with the placebo group (P = .04), with trends favoring rasagiline in digit span total and digit‐ordering tests. Verbal fluency total score showed a significant difference in favor of rasagiline (P = .038), with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections. The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score (P < .005). There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores. The monoamine oxidase type‐B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinsons disease with cognitive impairment.

Evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of ischaemic stroke.

Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with increased incidence of stroke in some populations, although contradictory results have been reported. The aim of this study was to determine the allelic frequency and the genotypic distribution for ACE gene polymorphism in Turkish patients with ischemic stroke compared to appropriate healthy controls and to correlate the genetic findings with stoke type. One hundred and eight patients with ischemic stroke versus 79 healthy controls were studied for the presence of ACE gene polymorphism detected by PCR. Genotypes were defined as DD, II and ID according to the presence of the D (deletion) and I (insertion) alleles. There was no statistically significant difference in either the genotypic distribution or allelic frequency between the patients versus healthy controls (chi2 = 0.105; df = 1; p = 0.430). There was also no significant difference for ACE genotype distribution and allelic frequency within the stroke group classified according to Bamford criteria (chi2 = 4.827; df = 3; p = 0.185). Our data supports lack of association between DD genotype and/or D allele and ischemic stroke or subtypes of ischaemic stroke in the Turkish population.

Short-wavelength automated perimetry in patients with migraine

BackgroundThe aim was to investigate short-wavelength sensitivity deficits in patients with migraine.MethodsFifteen migraine and 18 age-matched healthy volunteers with normal ophthalmologic examination participated in this study. Migraine characteristics were graded by the Migraine Disability Assessment Questionnaire (MIDAS). All participants underwent SWAP (short wavelength amplitude perimetry) testing using a Humphrey field analyzer; there was a 30-2 presentation pattern.ResultsShort wavelength amplitude perimetry parameters for mean deviation (MD; p<0.0001) and pattern standard deviation (PSD; p<0.0001) were significantly worse in the migraine group. In the migraine group 53.3%. of eyes had glaucoma hemi-field tests (GHT) outside normal limits and 10 of these had early glaucomatous visual field loss. Statistically significant correlations were found between frequency of migraine attacks and MD (p=0.02; r=0.56) and PSD (p=0.03; r=0.41) and also between the MIDAS score and MD (p=0.03; r=0.49) and PSD (p=0.04; r=0.51). In all migraine cases with early glaucomatous visual field defect a corresponding site of the head was predominantly involved in headache (p=0.03).ConclusionSome patients with severe migraine have earlier defects on SWAP suggesting a common vascular insult of glaucoma and migraine, and all migraine cases with high MIDAS scores should be further evaluated for early glaucomatous visual field defects using SWAP.

A case of multiple sclerosis with cerebral venous thrombosis: the role of lumbar puncture and high-dose steroids.

Case Report A 39-year-old woman presented with vertigo, vomiting and urgency incontinence of 10 days’ duration. Her medical history disclosed a first episode of left leg weakness lasting 1 month 2 years ago. She had no other systemic antecedents or cardiovascular risk factors. On admission, she presented left pyramidal and sensory signs together with limb ataxia. Her cranial magnetic resonance imaging (MRI) demonstrated lesions highly suggestive of a demyelinating disease. A clinical diagnosis of definite relapsing-remitting MS [4] with an Expanded Disability Status Scale (EDSS) score of 2.5 was made. An LP was performed with an atraumatic needle (18 G) on the day of admission and crebrospinal fluid (CSF) examination demonstrated the presence of oligoclonal bands with no other pathology. Consequently, pulse methylprednisolone of 1,000 mg per day for 5 days was started as an acute attack treatment, followed by 60 mg of prednisolone p.o. The patient was discharged home with partial recovery (EDSS score of 2.0) and on tapering doses of prednisolone. On the 10th day after LP and while on 50 mg of prednisolone, the patient experienced right arm weakness lasting 5 min. Twelve hours following this transient episode, she developed two consecutive, simple, partial, secondarily generalized seizures. Her neurologic evaluation revealed disorientation and somnolence, right homonymous hemianopia and right-sided pyramidal signs. Her new cranial MRI conFig. 1. T2-weighted cranial MRI showing a left cortical parietal infarct as well as periventricular hyperintense lesions compatible with MS plaques. Fig. 2. Cranial MRV demonstrating occlusion of the superior sagittal sinus.

Effects of Decompressive Surgery on Prognosis and Cognitive Deficits in Herpes Simplex Encephalitis

Herpes simplex encephalitis (HSE) is a serious viral infection with a high rate of mortality. The most commonly seen complications are behavioral changes, seizures and memory deficits. We report the case of a 37-year-old man with HSE in the right temporal lobe and a severe midline shift who was treated with acyclovir. The patient underwent anterior temporal lobe resection. Although HSE can cause permanent cognitive deficits, in this case, early surgical intervention minimized any deficit, as determined by detailed neuropsychological examination. Surgical decompression is indicated as early as possible in severe cases. This case report emphasizes the effect of surgical decompression for HSE on cognitive function, which has rarely been mentioned before.

The Effects of Quantum Energy Surgical Device and of Bipolar Coagulation: A Comparative Experimental Study

Summary.Summary. Objective: The quantum energy surgical device (QESD) employs an innovative, “no-touch” thermal coagulation, incision and evaporation technique in which thermal energy is delivered to tissue in the format of high-energy neutral argon gas atoms. The aim of this study is to compare QESD and bipolar coagulation (BC) through assessment of both haemostasis and histological damage to isolated femoral arteries of rats. Methods: Sxity rats were randomly divided into acute and short-term experimental groups. In the acute group (n=20) histopathological evaluation was performed immediately following coagulation, whereas in the short-term experimental group (n=20) the evaluation was performed 10 days later. Each sham group consisted of ten rats. Viewed under the surgical microscope, only normal-appearing, freshly sectioned, and bleeding femoral arteries were studied. Right femoral arteries subject to QESD coagulation, and left femoral arteries to BC. Haemorrhaging was controlled using the minimal coagulation time necessary to stop it. All vascular layers, including endothelium, internal elastic lamina, media and adventitia were examined histologically and ultrastructurally in a “blind” fashion to critically compare morphological damage due to QESD and BC. Results: Surgical haemostasis induced by QESD was found to be as safe as BC. Light microscopy revealed more marked histopathological changes in the BC than in the QESD group. These involved mainly the endothelial and medial compartments and, at the ultrastructural level, consisted of endothelial degeneration and exfoliation, irregularity of internal elastic lamina, degeneration, and loss of medial smooth muscle. Conclusion: The results indicate that QESD coagulation induces significantly less histological damage than does BC. Thus QESD coagulation is a safe, less tissue destructive, and equally effective method of haemostasis.

Dysexecutive syndrome: a specific pattern of cognitive impairment in systemic sclerosis.

Background and Purpose:Systemic sclerosis (SSc) is a connective-tissue disorder characterized by microvascular damage and tissue fibrosis. Although overt nervous system involvement is unusual in SSc, imaging studies have shown cerebral hypoperfusion. We evaluated cognitive functions in patients with SSc who had no history of neurological involvement, to seek cognitive impairment caused by the suggested cerebral hypoperfusion. Methods:We performed a comprehensive neuropsychological test battery on 31 patients with SSc and on 2 groups of age-adjusted, sex-adjusted, and education-adjusted controls: 15 patients with rheumatoid arthritis and 20 healthy volunteers. Results:The patients with SSc scored significantly worse on most of the measures of executive function than the 2 control groups (P<0.05). However, both patient groups did worse than the healthy controls on measures of attention and memory (P<0.005). Conclusions:Our results suggest that patients with SSc have a specific pattern of cognitive impairment: the dysexecutive syndrome. Attentional and memory problems, however, may arise from other confounders such as disease duration and chronic medication use. SSc may be a rare cause of vascular cognitive impairment.

PSYCHOTIC DEPRESSION: A PECULIAR PRESENTATION FOR MULTIPLE SCLEROSIS

Multiple sclerosis (MS) is frequently associated with a number of different psychiatric syndromes. Solely psychiatric syndrome may be the first clinical presentation of multiple sclerosis. We report a patient whose first attack was psychotic depression. The present case emphasizes that psychiatric symptoms can occur at any time during the course of the disease and, moreover, may be the presenting feature.