Sevinç Aktan

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.

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.

Autonomic dysfunction in multiple sclerosis: correlation with disease-related parameters.

Cardiovascular autonomic functions were investigated in a prospective, controlled study of 22 consecutive relapsing-remitting multiple sclerosis (MS) patients and 22 healthy subjects using 5 simple noninvasive tests and sympathetic skin response testing. Tests included the heart rate response to deep breathing, valsalva maneuver and standing, blood pressure response to standing and sustained hand grip, and were graded according to the Ewing and Clark classification as early, definite or severe impairment. The relationship between autonomic dysfunction and disease-related parameters such as the expanded disability status scale (EDSS) and disease duration was studied. Ninety percent of the patients had symptoms related with autonomic dysfunction, and 45.5 % had abnormal results in cardiovascular autonomic function testing with 4 patients also having abnormal sympathetic skin responses. Statistical analysis indicated that patients with a long disease duration rather than high EDSS carried a risk of autonomic involvement in MS. Both parasympathetic and sympathetic functions were impaired and this could have been easily overlooked by a standard EDSS follow-up. In this regard, autonomic function testing seems necessary in order to detect subclinical changes in MS patients and should be considered in outcome measures.

New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide.

Abstract Propranolol and primidone are widely used, effective agents in essential tremor although they are not tolerated by all patients. In the present study, the effectiveness of alprazolam, a triazole analog of benzodiazapine class, and acetazolamide, a carbonic anhydrase inhibitor, were investigated as symptomatic treatments for essential tremor. We studied 22 patients with essential tremor in a double-blind, cross-over, placebo-controlled design. The patients received in random order alprazolam, acetazolamide, primidone and placebo for four weeks, each separated by a two-week washout period. The study demonstrated that alprazolam was superior to placebo and equipotent to primidone, whereas there was no statistically significant difference between acetazolamide and placebo. The mean effective daily dose of alprazolam was 0.75 mg and there was not any troublesome side effect reported by the patients on alprazolam. Alprazolam can be used as an alternative agent in elderly essential tremor patients who can not tolerate primidone or propranolol.

Antiglutamatergic therapy in Alzheimer's disease – effects of lamotrigine

Summary. It has been proposed that excitotoxic damage by glutamatergic hyperactivity is responsible for neurodegeneration in Alzheimers disease. Lamotrigine (LTG) inhibits presynaptic glutamate release and is considered to be effective in treatment of other neurodegenerative disorders by its cerebroprotective properties. We used LTG in 11 patients with the diagnosis of probable Alzheimers disease. 300 mg/day administration of LTG improved word recognition, naming and depressed mood on Alzheimer Disease Assessment Scale (ADAS).

Leukotriene C4 and prostaglandin E2 activities in the serum and cerebrospinal fluid during acute cerebral ischemia.

Lipoxygenase pathway products of arachidonic acid (AA) metabolism (known as leukotrienes, LTs) are produced in the brain during pathologic conditions such as ischemia, hemorrhage, trauma, and seizure in which the release of AA is sustained by the activation of local phospholipases. The most common type of LT in the central nervous system is an LTC4 which is a highly potent vasoconstrictor leading to increase in vascular permeability. In this study, we compared the serum (S) and cerebrospinal fluid (CSF) prostaglandin E2 (PGE2) and LTC4 levels in 13 consecutively admitted patients with acute cerebral ischemia aged 55-80 years with 10 age-matched controls. Patients with previous glucocorticosteroid and antiinflammatory drug usage were not included in the study. S and CSF samples were drawn during the first 72 h of the attack, and samples were evaluated by bioassay. There was no significant difference in S PGE2 and LTC4 values, whereas a significant difference was observed between CSF PGE2 and LTC4 values as compared with the control group. The high levels of CSF PGE2 and LTC4-like activity in acute cerebral ischemia may indicate that these mediators have a role to play in cerebral edema. The CSF PGE2/LTC4 ratio was also found to be reduced in the ischemic group implying higher LTC4 synthesis than PGE2 synthesis. In the light of these findings, we suggest that use of a selective antagonist of LTs may be helpful in reducing the ischemic penumbra during acute cerebral ischemia by controlling the vasogenic edema.

Predictors of refractoriness in a Turkish status epilepticus data bank

Refractory status epilepticus (RSE) is known to constitute approximately 10-50% of all cases of status epilepticus (SE) and is associated with significant morbidity and mortality. In the present study, data from a prospectively collected SE database were analyzed. Patients with RSE (defined as a SE episode requiring a second line of intravenous treatment following intravenous phenytoin) were compared with patients with nonrefractory SE (NRSE); 290 episodes of SE were identified, of which 108 (38%) were defined as RSE. Univariate analysis revealed that age, female gender, SE type, SE duration, and acute etiology were associated with refractoriness, whereas electroencephalographic patterns were not. Nonconvulsive SE, which is probably associated with delays in treatment initiation, was a predictor of RSE, although it was not retained as a predictor in multivariate analysis. In the latter analysis, female gender (odds ratio: 1.815, 95% CI: 1.053-3.126) and acute etiology (odds ratio: 0.619, 95% CI: 0.429-0.894) were shown to be the only significant independent predictors of refractoriness.

The alterations of leukotriene C4 and prostaglandin E2 levels following different ischemic periods in rat brain tissue

Leukotrienes and prostaglandins are formed from arachidonic acid by activation of local phospholipases in pathological conditions such as cerebral ischemia, subarachnoid hemorrhage, cerebral tumors and seizures. These mediators, especially leukotrienes have a very potent vasoconstrictor effect on cerebral arteries. Experimental studies have shown that this effect, by increasing vascular permeability causes vasogenic edema that contributes to the ischemic penumbra. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of leukotriene C and prostaglandin E2 produced in the forebrain were measured and the effects of these mediators in prolonged ischemia were investigated. The results, in the first 4 min of ischemia, showed that the arachidonic acid metabolites, particularly, leukotriene C4, reached a peak in the ischemic cerebral tissue in association with leukocyte accumulation. Later in the 15th min, significant decreases in leukotriene C4 and prostaglandin E2 levels were seen. In the 1st and 4th h, probably due to the stimulation of the relevant enzymes by free oxygen radicals in the ischemic tissue; the levels increase again, returning to control values by the 12th h. It is concluded that the use of lipoxygenase inhibitors and free radical scavengers may be helpful to limit the infarct area in the first 4 h of ischemia.

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.

Computed Tomography and Magnetic Resonance Imaging in Three Patients with Tolosa-Hunt Syndrome

Three patients with Tolosa-Hunt syndrome were examined by computed tomography (CT) and magnetic resonance imaging (MRI). CT of the brain did not reveal any definite abnormality in any of the patients. MRI demonstrated an abnormal soft tissue area in the cavernous sinus in only 1 patient. There was clinical improvement after corticosteroid therapy. MRI is mandatory for demonstrating lesions in the cavernous sinus or in the superior orbital fissure in patients with THS.