Late spontaneous recanalization of symptomatic atheromatous internal carotid artery occlusion.

INTRODUCTION: Definitive treatment of symptomatic atheromatous internal carotid artery occlusion remains controversial, as far as in rare cases, late spontaneous recanalization has been seen. METHODS: We consecutively studied 182 patients (January 2003 to August 2012) with an ischemic stroke in the internal carotid artery territory and diagnosis of atheromatous internal carotid artery occlusion during hospitalization. FINDINGS: Seven patients presented a late spontaneous recanalization (>3 months) of the internal carotid artery. We described therapeutic attitude according to usual care in these patients. CONCLUSIONS: The authors attempt to highlight the unusual condition of recanalization after a symptomatic atheromatous chronic internal carotid artery occlusion. If these patients can be treated similar to patients with asymptomatic carotid pathology, then this needs to be clarified. However, due to the risk of ipsi- and contralateral ischemic strokes, revascularization techniques should be considered in certain cases. More studies are needed to establish the most appropriate therapeutical approach in order to avoid arbitrary treatment of these patients.

Long term evolution of patients treated in a TIA unit.

BACKGROUND: Transient ischemic attacks (TIA) entail a high risk of stroke recurrence, which depends on the etiology. New organizational models have been created, but there is not much information about the long-term evolution of patients managed according to these premises. Our aim is to refer the follow-up of patients attended according to our model of TIA Unit. METHODS: TIA Unit is located in the Emergency Department and staffed by vascular neurologists. Patients admitted during the Neurology night shift stayed in such Unit <48h with complete etiological study. Preventive treatment is instituted in patients discharged to a high resolution Neurology consult, in order to review in <2 weeks and subsequent follow-up. RESULTS: During a year 161 patients were attended, being admitted to the hospital 8.6%. A total of 1470 hospital days were avoided. Recurrence at 90 days was of 0.6%. Mean follow-up was 18.14 ± 8.02 months (0-34), total recurrence 6.2% (70% cardioembolic strokes). There were no complications derived from treatment. Cardiological events were recorded in 10.6%, neoplastic in 5%, cognitive impairment in 11%. There were 3 deaths unrelated nor to the stroke or its treatment. CONCLUSIONS: This model allows an early diagnosis and treatment of TIA, preventing recurrences of stroke in a long term. It detects atherothrombotic strokes, most of them admitted to the hospital, and it shows a greater difficulty for detecting all cardioembolic strokes. TIA Unit appeared to be safe in using anticoagulation therapy, as the follow-up shows. It shows the same quality of management than hospital admission, with a significant saving in hospital stays.

Oral anticoagulation in elderly patients as secondary prevention of cardioembolic strokes.

BACKGROUND: Stroke incidence increases with age. Atrial fibrillation (AF) is an important risk factor for ischemic stroke and its incidence also increases with age. However oral anticoagulant therapy (OAT) tends to be underused in the elderly population. METHODS: Elderly patients (> = 80 years) with an ischemic stroke admitted in our department between 1/7/2003 and 31/6/2005 were prospectively evaluated. Baseline characteristics, risk factors, treatment and etiology according to TOAST criteria were recorded. Patients treated with OAT were followed up in order to assess any side effect and stroke recurrence. Mean follow-up was of 19.5 months (7-45) from discharge. RESULTS: Sixty four out of a hundred and fifty nine elderly patients (40.25%) were classified as cardioembolic; mean age was 84.5 years (80-97) and 64.6% were women. AF had been previously identified in 60% of them (16.9% were on OAT and 40.6% on antiplatelet therapy). At discharge, 32 patients (49.2%) were on OAT. In the follow-up 4 patients (12.5%) suffered systemic haemorrhages (3 urinary, 1 gastrointestinal bleeding), with no change in their functional status. Mean INR in this group was 5.9 34567891011 and, in 3 of them, OAT was cancelled. No brain haemorrhages were recorded. Ischemic stroke recurred in 4 patients (INR < 1.8 in 3 of them; the other, INR 2.35). Three patients had died at the end of the follow-up, one of them as a consequence of ischemic stroke recurrence. DISCUSSION: Twenty eight point eight of stroke patients admitted in the period of study were >80 years. The high proportion of cardioembolic strokes in this age segment contrasts with the general underuse of OAT as antithrombotic prophylaxis. Our study suggests that OAT is a safe strategy when carefully prescribed, even for elderly patients.

The Sp1/Egr1-tandem repeat polymorphism in the 5-lipoxygenase gene promoter is not associated with late onset Alzheimer disease.

Arachidonate 5-lipoxygenase plays an important role in the synthesis of leukotrienes. Leukotrienes are inflammatory mediators, and inflammation has been implicated in the pathogenesis of Alzheimer disease. A polymorphism in the ALOX5 promoter consisting on 3 to 6 tandem-repeats of a Sp1/Egr1 binding motif (GGGCGG)n, has been related with the amount of gene expression. To verify the association between this polymorphism and the risk for late-onset Alzheimer disease we genotyped a total of 291 patients (mean age 74+/-7 y) and 300 controls (mean age 73+/-8 y). We found alleles of 3 to 6 repeats, and allele and genotype frequencies did not differ between patients and controls. These frequencies did not differ between patients according to the APOE genotype (epsilon 34 + epsilon 44 vs. epsilon 23 + epsilon 33). Together, our results indicate that the Sp1/Egr1-repeat polymorphism in the ALOX5 promoter is not a genetic marker for the risk of developing late-onset Alzheimer disease.

Myocyte enhancing factor-2A in Alzheimer's disease: genetic analysis and association with MEF2A-polymorphisms.

Polymorphisms at different genes have been proposed as determinants of the risk for developing late-onset Alzheimer's disease (LOAD). Among the several candidate genes are those that encode proteins involved in neuronal degeneration/survival. Studies of primary neuronal cultures supported that members of the myocyte enhancing factor-2 (MEF2) family of transcription factors have an anti-apoptotic effect, regulating the expression of proteins involved in neuronal survival and differentiation. We analysed the MEF2A gene in a total of 357 patients (mean age 72 years, range 60-97 years). Among others, a Pro279Leu in exon 8 and a polyglutamine (CAG) repeat polymorphisms in exon 12 were found. These variants were also genotyped in 495 healthy controls (>50 years old), and the frequencies were statistically compared. Eight patients were 279L (six P/L and two L/L), compared to only one control (2% vs. 0.2%; p=0.004, OR=11.32). There was a significantly higher frequency of 279L-carriers among APOE epsilon4+ (7/154=4.5%), compared to epsilon4- (1/203) (p=0.02). In conclusion, our work suggests that the variation at the MEF2A gene could be involved in the risk of developing LOAD. Because MEF2 has been related with neuronal survival, and the 279L allele has been related with a reduction in the transcriptional activation activity of MEF2A, the effect of this allele could be mediated through a down-regulation of antiapoptotic genes.

Mitochondrial DNA polymorphisms and risk of Parkinson's disease in Spanish population.

Mutations in mitochondrial DNA (mtDNA) have been implicated in the development of Parkinson's disease (PD). Mitochondrial function is necessary to supply the energy required for cell metabolism, and mutations in mitochondrial genes should have a deleterious effect in neuronal function. An association between several common mtDNA-polymorphisms and the risk of PD has been described. To test this association among Spanish patients, we genotyped 271 PD-patients and 230 healthy controls for 13 single-nucleotide polymorphisms (SNPs) through polymerase chain reaction (PCR) followed by digestion with a restriction enzyme. Alleles at eight of these SNPs define nine common European haplotypes, the mitochondrial haplogroups. In our population, no haplogroup showed significantly different frequencies between patients and controls. A significant association was found for the 4336T/C SNP (a polymorphism in the tRNA gln gene), with allele 4336C having a significantly increased frequency in PD-women compared to controls (OR=4.45; 95%CI=1.23-15.96; p=0.011). We also sequenced five of the complex I genes (ND1 to ND5) in the patients who were 4336C, and no mutation in these genes was found. We also found a significantly reduced frequency of 10398G in patients (p=0.009; OR=0.53), confirming a previously described protective effect for this allele in PD. In conclusion, we provided further evidence of the involvement of mitochondrial DNA variation in PD. In agreement with previous reports, we described a higher risk for PD among women with the mitochondrial 4336C allele in our population, and a protective effect for 10398G.

Chemokines (RANTES and MCP-1) and chemokine-receptors (CCR2 and CCR5) gene polymorphisms in Alzheimer's and Parkinson's disease.

Parkinson's disease (PD) is a complex disorder characterized by the progressive degeneration of dopaminergic neurons in the midbrain. Late-onset Alzheimer's disease (LOAD) is the most common cause of dementia in the elderly, affecting about 5% of the population older than 65 years. Several works have demonstrated the involvement of inflammation in the pathogenesis of both, PD and LOAD. Genetic susceptibility to develop PD and LOAD has also been widely recognised. Thus, functional polymorphisms at the genes encoding inflammatory proteins could influence the overall risk of developing these neurodegenerative disorders. We examined whether DNA-polymorphisms at the genes encoding chemokines MCP-1 (-2518 A/G) and RANTES (-403 A/G), and chemokine receptors 5 (CCR5, Delta32) and 2 (CCR2,V64I), were associated with the risk and/or the clinical outcome of LOAD and PD. A total of 200 PD, 326 LOAD, and 370 healthy controls were genotyped for the four polymorphisms, and genotype frequencies statistically compared. We did not find significant differences in the frequencies of the different genotypes between both groups of patients and controls. We conclude that the four DNA polymorphisms, which have been associated with several immuno-modulated diseases, did not contribute to the risk of PD or LOAD.

Spontaneous recanalization of acute internal carotid artery occlusion.

Little is known about the natural course of internal carotid artery occlusion and its possible recanalization. We present here a case of spontaneous recanalization of an acutely occluded internal carotid artery, angiographically reported, which later allowed the patient to benefit from surgical treatment. These and other similar cases raise the possibility of a more frequent recanalization of this artery than previously considered. We suggest routine follow-up of these patients to detect this eventuality, which could influence clinical outcome and secondary prophylaxis strategies.

Single-nucleotide polymorphisms in the promoter region of the PARKIN gene and Parkinson's disease.

Mutations in the PARKIN gene have been identified in families with recessively inherited Parkinson disease (PD). Common DNA-polymorphisms at the PARKIN gene could contribute to the risk for PD in the general population. Here we searched for DNA-polymorphisms in the PARKIN promoter. We found two single nucleotide polymorphisms (-324 A/G and -797 A/G). In order to analyse the association of PD with these and two previously described polymorphisms (1281 G/A, Asp394Asn, and 601 G/A, Ser167Asn) we genotyped 105 patients and 150 healthy controls. Allele and genotype frequencies for the four polymorphisms did not differ between patients and controls, or between patients with an early-onset (< or =40 years; n = 20) and a late-onset (>40 years; n = 85). According to our data, the genetic variation at the PARKIN gene (including promoter polymorphisms) did not contribute to the risk of developing PD in the general population.

Association between the TNFalpha-308 A/G polymorphism and the onset-age of Alzheimer disease.

Local inflammatory processes associated with amyloid plaques would contribute to the progression of late-onset Alzheimer disease (LOAD). Tumor necrosis factors alpha (TNF(alpha)) and beta (LT(alpha)) are inflammatory cytokines involved in the local immune response occurring in the central nervous system of LOAD patients. Genetic variation at these genes could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 315 LOAD patients and 400 healthy controls for DNA-polymorphisms in the genes encoding TNF(alpha) (-308 G/A, -238G/A) and LT(alpha) (Asn26Thr). Carriers of -308A showed a mean age at onset 3 years younger than noncarriers of this allele (P = 0.019). Our data suggest an effect of the TNF(alpha)-308 polymorphism on the age at onset of late AD. This represents additional evidence of the importance of genetic variation at the proinflammatory components in the origin and progression of this common neurodegenerative disease.