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Seizure 01/2013; · 1.80 Impact Factor
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ABSTRACT: Lacosamide (LCM) is a newer antiepileptic drug with a favorable safety profile used in partial epilepsy as adjunctive therapy. The most common side effects include dizziness, headache, confusion, diplopia, nausea, nasopharyngitis, and vomiting. Although sporadic cases of drug-induced psychosis have been reported for some antiepileptic drugs, this was not the case for LCM. We describe the first case of LCM-induced psychosis in a patient with drug-resistant partial epilepsy during the first week of treatment initiation, stressing the importance of clinicians remaining alert for abnormal behavioral symptoms.
Clinical neuropharmacology 01/2013; 36(1):27-28. · 2.35 Impact Factor
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ABSTRACT: Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies.
International journal of cardiology 07/2012; · 7.08 Impact Factor
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ABSTRACT: Metabolism of valproic acid, a widely used drug, is only partially understood. It is mainly metabolized through glucuronidation and acts as a substrate for various UDP-glucuronosyltransferases (UGTs). UGTs metabolizing valproic acid in the liver are UGT1A3, UGT1A4, UGT1A6, UGT1A9 and UGT2B7, with UGT1A6 and UGT2B7 being the most prominent. Polymorphisms in genes expressing these enzymes may have clinical consequences, regarding dosing, blood levels of the drug and adverse reactions. Not all genes are well studied and studies, where they exist, report conflicting results. Prevalence of polymorphisms and various haplotypes is also of great importance, as it may suggest different therapeutic approaches in various populations. Presented here is a review of currently known polymorphisms, their functional impact, when known, and their prevalence in different populations, highlighting the current state of understanding and areas where there is a lack of data and suggesting new perspectives for further research.
Pharmacogenomics 07/2012; 13(9):1055-71. · 3.97 Impact Factor
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ABSTRACT: Raising interest towards genes implicates the effect of estrogen receptor-alpha (ESR1) gene on cerebrovascular disease, but data are lacking regarding the effect of estrogen receptor-beta (ESR2) gene. We assessed the hypothesis that AluI (G/A) polymorphism of the ESR2 gene (rs 4986938) is associated with ischemic stroke in a Caucasian population. Four hundred twenty four consecutive stroke patients and 430 age and gender-matched controls were enrolled in three stroke centers in Greece over one-year period. Patients and controls were compared in regard to the prevalence of the aforementioned polymorphism. No association was found between variations in the ESR2 gene and risk of stroke or stroke subtype in men and women. Of note, a gender-specific association of G allele with the onset of stroke at a younger age in male patients was found (63.68 ± 12.687 years in G allele (GG+AG) carriers vs. 68.95 ± 10.757 years in non-carriers (AA), p=0.008). Further population independent studies are needed to establish the role of ESR2 gene polymorphisms in relation to ischemic stroke in both genders. Such studies could lead to ERβ agonists being validated in individuals with certain genotypes and/or alleles towards the development of efficient strategies to preventing ischemic stroke in both men and women.
Journal of the neurological sciences 02/2012; 316(1-2):126-30. · 2.32 Impact Factor
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ABSTRACT: To establish an empirical systematic approach for the management of brain metastases from a variety of cancers.
The English literature was reviewed from 2000 to 2011 and all clinical trials (phase II, phase III and retrospective studies) regarding therapy of brain metastases were selected for more detailed review. Some key articles published prior to 2000 were also included in the review as are supplemental recommendations based on our clinical experience.
Patients with brain metastases from small cell lung cancer (SCLC) at the initial cancer diagnosis can be treated with concomitant whole-brain radiation therapy (WBRT) and chemotherapy or first with chemotherapy followed by WBRT. In all other cases, brain metastases are currently treated independently of the management of the extracranial disease with surgery or radiosurgery followed by WBRT. In radioresistant tumors (melanoma, sarcoma, renal cell carcinoma), WBRT may be omitted initially but administered at recurrence. Where surgery or radiosurgery is not an option for patients, WBRT should be administered. Prophylactic WBRT should be given in patients with SCLC and considered in patients with non-small cell lung cancer. Apart from its use in SCLC, chemotherapy for the treatment of brain metastases is reserved for patients enrolled in clinical trials.
Brain metastases should be treated aggressively and independently of the primary site tumor especially if the performance status of the patient is good. The role of chemotherapy should be addressed in the context of clinical trials.
Cancer Chemotherapy and Pharmacology 01/2012; 69(1):1-13. · 2.83 Impact Factor
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ABSTRACT: Endothelial nitric oxide synthase (eNOS) G894T polymorphism has been previously associated with vascular diseases including stroke, but often with conflicting results. Experimental evidence suggests that some eNOS modalities may be important in preventing stroke, while others may be important during the dynamic inflammatory processes triggered at the acute phase of stroke. Thus, we examined the possible association of eNOS G894T variation with stroke severity and functional outcome.
One hundred and eight consecutive patients with first ever acute atherothrombotic or lacunar stroke, and 193 stroke-free subjects were recruited. Demographic data, medical history, and vascular risk factors were collected. Assessments for stroke severity and functional outcome were carried out on admission and at one month post-stroke, respectively. eNOS G894T genotypes were produced using a standard restriction-fragment-length polymorphism technique.
eNOS G894T polymorphism genotypic distributions did not differ between stroke patients and controls, as well as between each stroke subtype and controls. Carriage of T allele (GT and TT genotypes versus GG) was not significantly associated with either stroke severity or functional outcome in the univariate analysis. However, after accounting for age, gender and stroke severity, the presence of T allele strongly predicted poor outcome [odd ratio 8·49 (95% confidence intervals 1·57-46·0)]. Further adjustments for other important confounders could not alter the above significant association.
Carriers of the eNOS 894T allele are at increased risk for adverse outcome at one month post-stroke, independently of severity and other confounding factors. Therapeutic interventions targeting patients with this unfavorable mutation may be an appealing approach.
Neurological Research 10/2011; 33(8):835-40. · 1.52 Impact Factor
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ABSTRACT: Multiple sclerosis (MS) may be associated with reduced bone mass and higher frequency of osteoporosis. Femoral and spinal bone mineral density (BMD) in 70 ambulatory MS patients (46 females and 24 males) was compared with 100 sex-, age-, and BMI-matched control individuals. BMD was reduced in male patients (lumbar spine 0.976 ± 0.114 g/cm(2) compared with 1.059 ± 0.147 g/cm(2) in controls, p = 0.024, total hip 0.946 ± 0.136 g/cm(2) compared to 1.036 ± 0.118 g/cm(2) in controls, p = 0.008, femoral neck 0.812 ± 0.136 g/cm(2) compared with 0.887 ± 0.135 g/cm(2) in controls p = 0.042), and only in the total hip in female patients (0.88 ± 0.127 g/cm(2) compared with 0.935 ± 0.112 g/cm(2) in controls, p = 0.018). Multivariate analysis demonstrated that the predominantly affected site was the hip. MS patients exhibit increased frequency of low bone mass compared with controls. Further studies should assess the etiologic factors and employ appropriate therapies.
Neurological Sciences 05/2011; 32(5):819-24. · 1.32 Impact Factor
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ABSTRACT: The standard therapy for newly diagnosed malignant gliomas comprises surgery, radiotherapy, and commonly temozolomide chemotherapy. For recurrent or progressive disease after temozolomide failure, there is no consensus and only limited options for chemotherapy.
We reviewed the English literature for phase II trials of therapies for recurrent malignant glioma conducted between January 2000 and September 2010. The search was supplemented by a review of articles published prior to 2000 on chemotherapy regimens that had shown activity on recurrent gliomas.
To guide practice in the general oncology setting, an algorithm was constructed according to the activity of the reported chemotherapies at the time of writing. Some molecular studies performed on tumor tissue may help guide the selection of chemotherapy. Methylated MGMT in tumor tissue correlates with increased sensitivity to alkylating agents such as fotemustine or other nitrosoureas. Depending on MGMT status and bone marrow reserve, treatment with fotemustine, bevacizumab, bevacizumab with irinotecan, or cis-retinoic acid (cRA), might be of value.
Unfortunately, progress in the development of new and more effective chemotherapy agents has been very limited and leaves the clinician treating high-grade glioma patients at relapse with few good options. The suggested algorithm is our objective evaluation of the currently existing knowledge. Hopefully, the ongoing phase II and III trials will provide us the needed chemotherapy agents in the years to come.
Cancer Chemotherapy and Pharmacology 03/2011; 67(5):971-83. · 2.83 Impact Factor
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ABSTRACT: Patients who present with multiple cerebral tumors are usually considered as having metastatic disease. If they have a history of a primary cancer in another site, the brain tumors are considered metastases and are usually managed with standard whole-brain radiotherapy. If no primary cancer site is known, a diagnostic work-up is performed, but if no primary site is found, they are still considered as brain metastases from an unknown primary site. Thus, such patients can either have brain biopsy (recommended) for further diagnostic consideration or, occasionally, they can be treated with whole-brain radiotherapy, depending on the age, performance status and wish of the patient. However, in some of these patients the multiple brain tumors represent multifocal glioma rather than metastases, resulting in incorrect treatment. In such cases, various MRI characteristics may be helpful in directing towards the correct diagnosis. Thus, patients who present with multiple brain tumors should not always be considered to have metastatic disease even if they have a previous diagnosis of systemic cancer, and multifocal glioma should be ruled out.
Oncology 03/2011; 79(3-4):306-12. · 2.27 Impact Factor
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ABSTRACT: We examined the association of the NG011648 polymorphism (insertion/deletion) of the angiotensin-converting enzyme (ACE) gene with ischaemic stroke occurrence, subtype of ischaemic stroke and ischaemic stroke patients' gender. Patients with first ever ischaemic stroke were recruited prospectively in a period of 18 months. Controls were matched with the patients for age, gender, and known risk factors for stroke. Demographic data, medical history, and vascular risk factors were collected. Genotypes were determined by polymerase chain reaction (PCR) and restriction enzyme analysis. Stroke and control groups were compared in regard to the prevalence of the NG011648 polymorphism. One hundred and seventy-six patients with ischaemic stroke and 178 controls were recruited and genotyped for NG011648 polymorphism (I/D) of the ACE gene. No significant difference in allele and genotype distributions emerged between control and patient groups, nor in the two subtype groups of lacunars and large artery atherosclerosis. After the data were stratified by gender, a low incidence of II homozygosity in female patients versus female controls (p = 0.05) and male patients (p = 0.013, Z score: -2.49) was found. Our results indicate that I/D polymorphisms may have a role in stroke onset, in respect to gender, with a possible favourable effect of II genotype in females.
Journal of Renin-Angiotensin-Aldosterone System 03/2011; 12(4):510-5. · 2.44 Impact Factor
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ABSTRACT: Gliomas are tumors of glial origin formed in the central nervous system and exhibit profound morphological and genetic heterogeneity. The etiology of this heterogeneity involves an interaction between genetic alterations and environmental risk factors. Scientific evidence suggests that certain natural dietary components, such as phytoestrogens, flavonoids, polyunsaturated fatty acids, and vitamins, may exert a protective effect against gliomas by changing the nature of the interaction between genetics and environment. Similarly, certain antiinflammatory drugs and dietary modifications, such as methionine restriction and the adoption of low-calorie or ketogenic diets, may take advantage of glioma and normal glial cells' differential requirements for glucose, methionine, and ketone bodies and may, therefore, be effective as part of preventive or treatment strategies for gliomas. Treatment trials of glioma patients and chemoprevention trials of individuals with a known genetic predisposition to glioma using the most promising of these agents, such as the antiinflammatory drugs curcumin and gamma-linolenic acid, are needed to validate or refute these agents' putative role in gliomas.
Nutrition and Cancer 02/2011; 63(2):174-84. · 2.78 Impact Factor
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ABSTRACT: We describe a 17-year-old Caucasian adolescent with ulcerative colitis who presented with cerebral venous sinus thrombosis. Laboratory investigation revealed low protein S levels. With successful management the patient remained without neurologic sequalae. Although there may be an association between ulcerative colitis and cerebral venous sinus thrombosis, the exact pathophysiologic mechanism remains unknown.
Brain & development 01/2011; 33(1):49-51. · 1.74 Impact Factor
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ABSTRACT: Polymorphisms of the vitamin D receptor (VDR) gene have been linked to both multiple sclerosis (MS) and osteoporosis. We examined the frequency of the Taq-I and Bsm-I polymorphisms of the vitamin D receptor (VDR) gene in 69 patients with MS and 81 age and sex-matched healthy individuals. Genotyping of Taq-I (rs731236) and Bsm-I (rs1544410) was performed using TaqMan SNP Genotyping Assay. All patients and controls had determination of body mass index (BMI), bone mineral density (BMD) and smoking history.
The mean age of patients was 39 ± 10.5 years compared to 38.7 ± 10.7 years of the controls (p = 0.86), the BMI was 24.8 ± 4.2 kg/m2 compared to 25.7 ± 4.8 kg/m2 of the controls (p = 0.23), the BMD in the lumbar spine 0.981 ± 0.15 compared to 1.025 ± 013 of the controls (p = 0.06) and the total hip BMD was 0.875 ± 0.14 compared to 0.969 ± 0.12 of the controls (p < 0.001). There were no differences of the Taq-I (TT, CT, CC) and Bsm-I genotypes (GG, GA, AA) and allelic frequencies between MS and control individuals. Multivariate analysis also failed to show any association of the Taq-I and Bsm-I polymorphisms and MS or sex, BMI, BMD and smoking history.
This study suggests that the Taq-I and Bsm-I polymorphisms of the VDR gene are not associated with MS risk, BMI or BMD in the Greek population studied.
Journal of Negative Results in BioMedicine 01/2011; 10:3. · 1.47 Impact Factor
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ABSTRACT: Background. The role of genetic factors in the predisposition to develop ischemic stroke has been assessed by previous studies. The main goal of the current study was to determine any possible role of TNF-857C>T, TNFRSF1A36A>G, and TNFRSF1B676T>G polymorphisms in risk for stroke. Materials and Methods. One hundred seventy-three patients with first ever ischemic stroke of solely atherosclerotic etiology in Northwest Greece and a control group of 179 healthy unrelated subjects were evaluated. Results. TNFα-857TT, TNFR136AA, and TNFR2676TT genotypes were significantly increased in the patient group compared to controls (P = .008, OR = 2.47 (1.26–4.84), P = .005, OR = 1.97 (1.22–3.17), and P = .003, OR = 2.2 (1.43–3.37), resp.). In addition, the TNFR136A and the TNFR2676T alleles were found significantly increased in patients compared to controls (P = .009, OR = 1.48 (1.1–2) and P = .001, OR = 1.75 (1.25–2.46), resp.). Conclusion. The high incidence of these genotypes and alleles in patient group suggests that they are potentially predisposing factors for stroke in the Greek population studied. Large-scale multicenter controlled studies are needed to verify these polymorphisms effects on stroke susceptibility.
SAGE-Hindawi Access to Research Stroke Research and Treatment. 01/2011; 5.
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ABSTRACT: Background. The role of genetic factors in the predisposition to develop ischemic stroke has been assessed by previous studies. The main goal of the current study was to determine any possible role of TNF-857C>T,TNFRSF1A36A>G, and TNFRSF1B676T>G polymorphisms in risk for stroke. Materials and Methods. One hundred seventy-three patients with first ever ischemic stroke of solely atherosclerotic etiology in Northwest Greece and a control group of 179 healthy unrelated subjects were evaluated. Results. TNFα-857TT, TNFR136AA, and TNFR2676TT genotypes were significantly increased in the patient group compared to controls (P = .008, OR = 2.47 (1.26-4.84), P = .005, OR = 1.97 (1.22-3.17), and P = .003, OR = 2.2 (1.43-3.37), resp.). In addition, the TNFR136A and the TNFR2676T alleles were found significantly increased in patients compared to controls (P = .009, OR = 1.48 (1.1-2) and P = .001, OR = 1.75 (1.25-2.46), resp.). Conclusion. The high incidence of these genotypes and alleles in patient group suggests that they are potentially predisposing factors for stroke in the Greek population studied. Large-scale multicenter controlled studies are needed to verify these polymorphisms effects on stroke susceptibility.
Stroke research and treatment. 01/2011; 2011:920584.
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ABSTRACT: Recent literature suggests a genetic component for non-arteritic anterior ischemic optic neuropathy (NAION). We examined the association of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene, of the M235T polymorphism of the angiotensinogen gene, and of the A1166C polymorphism of the angiotensin II type 1 receptor gene with NAION.
Forty-seven patients with NAION and 76 controls, age- and gender-matched, were recruited and genotyped for renin-angiotensin-aldosterone system (RAAS) genes. Genotypes were determined by polymerase chain reaction and restriction enzyme analysis. NAION and control groups were compared in regard to the prevalence of renin-angiotensin-aldosterone system polymorphisms, and further stratified by age and gender.
NAION occurrence was not associated with the M235T polymorphism of the angiotensinogen gene and the A1166C polymorphism of the angiotensin II, type 1 receptor gene. Regarding the angiotensin-converting enzyme insertion/deletion polymorphism, our findings suggest that the II genotype could be a risk factor for NAION in younger male patients when compared to all cases and controls (p=0.033, odds ratio=5.71, confidence interval=1.152¨C28.35 and p=0.03, odds ratio=5.33, confidence interval=1.17¨C24.31 respectively). Furthermore I allele was present in all male patients younger than 55 years, making this allele a likely predisposing factor for NAION in young males.
Since NAION may occur when compromised watershed microcirculation is combined with insufficient autoregulation of systematic circulation, polymorphisms of genes involved in systematic circulation, such as the RAAS genes, may be associated with NAION occurrence. Large-scale, multicentered, controlled prospective studies are needed to further explore the effects of RAAS polymorphisms or other genetic factors on NAION susceptibility.
Molecular vision 01/2011; 17:1254-60. · 2.20 Impact Factor
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ABSTRACT: Nonarteritic anterior ischemic optic neuropathy (NAION) is associated with vascular risk factors and a genetic predisposition for NAION. In this study, we examined the potential association of endothelial nitric oxide synthase (eNOS) G894T polymorphism with NAION. For this, 45 patients (29 men and 16 women) and 193 controls (122 men and 71 women) were enrolled prospectively and genotyped for eNOS genes. Genotypes were determined by polymerase chain reaction and restriction enzyme analysis. The prevalence of eNOS polymorphisms was estimated in NAION patients and controls. Genotype frequencies were estimated with chi-square test, and odds ratios were calculated. We found that eNOS G894T polymorphism is not associated with NAION occurrence as the genotype and allele frequencies were not significantly different between the control and patient groups (TT vs. GG + GT: P = 0.646 and T vs. G: P = 0.86). The precise mechanism of NAION occurrence has not been elucidated yet; since NAION may occur when a compromised watershed microcirculation is combined with insufficient autoregulation of systematic circulation, other alterations in the eNOS gene or polymorphism of genes involved in systematic circulation may be associated with NAION occurrence.
Visual Neuroscience 11/2010; 27(5-6):183-5. · 2.23 Impact Factor
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ABSTRACT: Parkinson's disease (PD) consists of loss of pigmented dopamine-secreting neurons in the pars compacta of the midbrain substantia nigra. These neurons project to the striatum (putamen and caudate nucleus) and their loss leads to alterations in the activity of the neural circuits that regulate movement. In a simplified model, two dopamine pathways are involved: the direct pathway, which is mediated through facilitation of the D(1) receptors, and the indirect pathway through D(2) receptors (inhibitory). Positron emission tomography (PET) tracers to image the presynaptic sites of the dopaminergic system include 6-[(18)F]FDOPA and 6-[(18)F]FMT, [(11)C]dihydrotetrabenazine, [(11)C]nomifensine and various radiolabelled cocaine derivatives. Postsynaptically, for the dopamine D(1) subtype the most commonly used ligands are [(11)C]SCH 23390 or [(11)C]NNC 112 and for the D(2) subtype [(11)C]raclopride, [(11)C]MNPA and [(18)F]DMFP. PET is a sensitive and specific non-invasive molecular imaging technique that may be helpful for evaluation of PD and its differential diagnosis from other parkinsonian syndromes.
European Journal of Nuclear Medicine 08/2010; 37(8):1594-603. · 4.53 Impact Factor
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ABSTRACT: Paraneoplastic neurological syndromes are immune-mediated effects of cancer that involve the nervous system and are associated with various anti-neuronal antibodies. They can be associated with several cancers such as lung, gynecologic, thymic, testicular and others, but the diagnosis of cancer often becomes a challenge, since paraneoplastic neurological syndromes usually precede the cancer presentation by months or even years. Furthermore, even when the cancer develops, the tumor size remains small and usually undetectable by conventional diagnostic tests and imaging. Positron emission tomography imaging may be an adjunct to timely diagnosis of the occult malignancy in order to employ the specific cancer treatment. Furthermore, positron emission tomography can assess the extent of the functional abnormality in the brain and monitor its response to treatment.
Oncology 04/2010; 78(2):150-6. · 2.27 Impact Factor
