Aleksandra Golenia

Periodontitis affects neurological deficit in acute stroke.

BACKGROUND AND PURPOSE Periodontitis is an independent risk factor for ischaemic stroke, but its influence on stroke severity has not been investigated yet. We studied the association of advanced periodontitis or edentulousness with neurological deficit on admission and short-term outcome of stroke patients. METHODS The study included 169 patients with ischaemic stroke. The neurological deficit on admission was evaluated using the NIH stroke scale (NIHSS). The outcome at discharge was assessed using the modified Rankin scale (mRS) and the Barthel Index (BI). The clinical attachement level (CAL), the distance between cemento-enamel junction and the probed base of periodontal pocket, was recorded for each tooth at six sites. Advanced periodontitis was defined as CAL≥6mm in at least one measured site. RESULTS Patients with advanced periodontitis or edentulousness were older than those with no or mild periodontitis (71.4years vs. 60.1; p<0.001), had greater neurological deficit on admission (8.9 vs. 5.7; p=0.01) and worse outcome at hospital discharge measured in the mRS (2.2 vs. 1.4; p=0.009). The presence of advanced periodontitis or edentulousness was independent risk factor for greater NIHSS on admission (p=0.025), after adjusting for age, gender and the studied risk factors. The logistic regression model, however, showed that stroke severity on admission but not advanced periodontitis or edentulousness, affected the outcome of stroke patients. CONCLUSIONS Advanced periodontitis or edentulousness in patients with ischaemic stroke is associated with greater neurological deficit on admission.

The –A162G polymorphism of the PON1 gene and the risk of sporadic amyotrophic lateral sclerosis

BACKGROUND AND PURPOSE Sporadic amyotrophic lateral sclerosis (sALS) is a devastating neurodegenerative disease, which results from complex genetic and environmental interactions. Recent studies have reported an association between several polymorphisms of the PON1 and PON2 genes and risk of sALS. The aim of the present study was to identify an association between the -A162G polymorphism of the promoter region of the human PON1 gene and the risk of sALS in a Polish population. MATERIAL AND METHODS We included 259 patients with a diagnosis of definite or probable sALS (76 bulbar onset, 183 limb onset) and 694 healthy controls matched for age and sex. The diagnosis of ALS was established according to El Escorial criteria. The polymorphism was studied by Single Nucleotide Polymorphism Real-Time Polymerase Chain Reaction analysis. RESULTS No overall difference in the PON1 -A162G geno-type and allele distribution was seen between cases and controls (all p > 0.05). There was, however, a difference in the A allele frequency when the bulbar onset group was compared to the controls (p = 0.03), but this significance disappeared after the Bonferroni correction. CONCLUSIONS The results did not show that the -A162G polymorphism of the PON1 gene is a risk factor of sALS in a Polish population; it may affect, however, bulbar onset of the disease.

The FGA Thr312Ala polymorphism and risk of intracerebral haemorrhage in Polish and Greek populations.

BACKGROUND AND PURPOSE Spontaneous intracerebral haemorrhage (ICH) is the most fatal form of stroke with the highest morbidity and disability rate of all stroke types. Recent data suggest that the genetic background has a sizeable and mostly undiscovered effect on the brain haemorrhage risk. Since the coagulation system is crucial to ICH pathology, we studied the significance of the FGA Thr312Ala polymorphism in two European populations. MATERIALS AND METHODS We genotyped 550 and 224 controls as well as 261 and 242 stroke patients in Polish and Greek populations, respectively. The ICH diagnosis was confirmed by computed tomography. The FGA Thr312Ala polymorphism was analysed using real-time polymorphism chain reaction. RESULTS Both crude and multivariable regression analyses showed that the studied polymorphism is a protective factor in the Polish population under the dominant and additive models of inheritance. Those results did not replicate in the Greek population. The meta-analysis of results from the Polish and the Greek populations proved that FGA Thr312Ala polymorphism affects the risk of ICH in the dominant model of inheritance. CONCLUSIONS The FGA Thr312Ala polymorphism affects a risk for ICH in the Polish but not in the Greek population. An advanced meta-analysis of well-designed studies with a significant number of cases might provide useful information of novel polymorphisms, including the FGA Thr312Ala polymorphism, and their role in ICH pathology.

The AGTR1 gene A1166C polymorphism as a risk factor and outcome predictor of primary intracerebral and aneurysmal subarachnoid hemorrhages

Associations between the angiotensin II type 1 receptor (AGTR1) gene A1166C polymorphism and hypertension, aortic abdominal aneurysms (as a risk factor) as well as cardiovascular disorders (as a risk factor and an outcome predictor) have been demonstrated. We aimed to investigate the role of this polymorphism as risk factors and outcome predictors in primary intracerebral hemorrhage (PICH) and aneurysmal subarachnoid hemorrhage (aSAH). We have prospectively recruited 1078 Polish participants to the study: 261 PICH patients, 392 aSAH patients, and 425 unrelated control subjects. The A1166C AGTR1 gene polymorphism was studied using the tetra-primer ARMS-PCR method. Allele and genotype frequencies were compared with other ethnically different populations. The A1166C polymorphism was not associated with the risk of PICH or aSAH. Among the aSAH patients the AA genotype was associated with a good outcome, defined by a Glasgow Outcome Scale of 4 or 5 (p<0.02). The distribution of A1166C genotypes in our cohort did not differ from other white or other populations of European descent. In conclusion, we found an association between the A1166C AGTR1 polymorphism and outcome of aSAH patients, but not with the risk of PICH or aSAH.

Catalase activity in blood fractions of patients with sporadic ALS

BACKGROUND Oxidative stress may be a key element in pathogenesis of sporadic amyotrophic lateral sclerosis (sALS). Several studies proved that markers of peroxidation of lipids, proteins or nucleic acids are increased in postmortem tissue of sALS patients. However, much less is known about enzymatic antioxidant defense mechanism in sALS. OBJECTIVES The aim of the study was to assess catalase (CAT) activity that is implicated in the defense against oxidative stress, in three blood fractions, i.e. erythrocytes, plasma and serum of sALS patients and healthy controls. METHODS Altogether 46 sALS patients and 54 controls were enrolled in the study. CAT activity was estimated using a commercially available assay kit. RESULTS CAT activity in erythrocytes of sALS patients was significantly decreased compared to neurologically healthy controls (p=0.04), whereas CAT activity in plasma and serum was similar in both studied groups. CONCLUSIONS CAT activity in erythrocytes, in contrast to other blood fractions is reduced in sALS cases as compared to controls, which may indirectly indicate that antioxidant defense system in erythrocytes is involved in pathogenesis of sALS.

Lack of association between VEGF gene polymorphisms and plasma VEGF levels and sporadic AL

The connection between the AAG/AAG and AGG/AGG haplotypes of the 3 single nucleotide polymorphisms (SNPs) (−2578C/A, −1154G/A, and −634G/C) of the vascular endothelial growth factor (VEGF) gene and sporadic amyotrophic lateral sclerosis (sALS) was documented in some, but not all populations.1 It was also shown that plasma VEGF levels in patients with sALS were significantly lower than in the controls.1 A recent meta-analysis comprising 7,082 participants did not confirm the association between risk haplotypes and sALS.2 Other studies did not confirm an association between plasma or serum VEGF levels and the risk of sALS.3,–,5 We studied the significance of the AAG/AAG and AGG/AGG haplotypes of the 3 SNPs of the VEGF gene as well as the significance of plasma VEGF levels in Polish patients with sALS. ### Methods. We included 271 unrelated patients with definite or probable sALS (El Escorial Criteria) admitted to the MND Clinic, Jagiellonian University, Poland. The controls consisted of 464 age- and gender-matched …

Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome

BACKGROUND Activation of Toll-like receptor 4 (TLR4) contributes to brain injury and poor outcome after cerebral ischemia. The expression of this receptor on monocytes is increased in patients with acute ischemic stroke. Endotoxin is an endogenous ligand for TLR4. The aim of our study was to determine if plasma endotoxin activity is increased in stroke patients and correlates with functional outcome. METHODS We included 88 patients with ischemic stroke (median age: 71, 56.8% men) and 59 age-matched controls. Plasma endotoxin activity and level of proteins regulating endotoxin interaction with TLR4 (LPS binding protein - LBP and sCD14) were measured in blood samples taken at day 1 (within 24h after stroke symptoms onset), 3 and 6. Short-term functional outcome was assessed at day 14 using modified Rankin Scale. Unfavourable outcome was defined as modified Rankin Scale score>2. RESULTS Compared to controls, stroke patients had higher plasma endotoxin activity on day 1 (median: 0.39 vs 0.32EU/mL, P=0.03) as well as higher LBP (median: 18.7 vs 11.5μg/mL, P<0.01) and sCD14 level (median: 1330 vs 1070ng/mL, P<0.01). Plasma LPS activity and levels of LBP and sCD14 significantly rose during stroke. Higher LPS activity measured on day 6 was associated with unfavourable outcome (OR: 3.94, 95%CI: 1.03-15.02, P=0.04, adjusted for age and stroke severity). CONCLUSIONS Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome.

Sympathetic vascular response to facial cooling is increased in flail phenotypes of amyotrophic lateral sclerosis

Abstract Objective: To assess cardiovascular responses to cold face test (CFT) in patients with classic-onset ALS (bulbar or limb onset, ALS-C) and in patients with flail arm and flail leg phenotypes (FA/FL). Methods: In 18 ALS-C, eight FA/FL patients and 10 age-matched controls we continuously monitored heart rate (HR), systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) during two-minute baseline and one-minute cold stimulus application. HR and BP responses to CFT were calculated as differences between the peak responses and baseline values (dHR, dSBP, dDBP, dMBP), as percent changes from baseline (dHR%, dSBP%, dDBP%, dMBP%), and also latencies and durations of HR and BP responses were assessed (LatHR, tHR, LatBP, tBP). Results: There were no differences in baseline values of HR, SBP, DBP and MBP among ALS-C, FA/FL and controls (p > 0.05). A decrease in HR and increases in SBP, DBP and MBP were observed in all subjects (p < 0.05). However, in FA/FL, the magnitude of BP responses, i.e. dSBP, dSBP%, dDBP, dMBP, and dMBP% were significantly higher than in controls. Moreover, these BP responses occurred with a significantly shorter latency in FA/FL than in controls and ALS-C. Furthermore, duration of the BP changes was significantly longer in FA/FL than in ALS-C. In contrast, ALS-C patients had a significantly longer LatHR and shorter tHR than healthy persons. However, no significant differences were observed in dHR or dHR% among the three groups. Conclusions: Sympathetic vascular response to facial cooling is increased in flail phenotypes of ALS.

Association between C677T polymorphism of MTHFR gene and risk of amyotrophic lateral sclerosis: Polish population study and a meta-analysis

OBJECTIVE Genetic factors play a role in pathogenesis of amyotrophic lateral sclerosis (ALS). A few studies demonstrated that the TT genotype of C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene can increase the risk of sporadic ALS. The aim of our study was to determine the relationship between C677T polymorphism of MTHFR gene and the risk of sporadic ALS in Polish population and to perform the meta-analysis assessing the significance this polymorphism for the risk of ALS in Caucasian population. METHODS We included 251 patients with ALS and 500 control subjects recruited from Polish population and performed the meta-analysis of published data from Caucasian population. MTHFR C677T polymorphism was genotyped using a TaqMan assay and 7900HT Fast real Time PCR System. RESULTS The frequency of genotypes did not differ significantly between Polish ALS patients and control subjects (CC: 45.0 vs 45.8%, CT: 48.2 vs 45.0%, TT: 6.8 vs 9.2%, P=0.46). The meta-analysis including 863 ALS patients and 1362 controls revealed that TT genotype increases the risk of sporadic ALS in Caucasian population. CONCLUSION Although we did not find the association between C677T polymorphism of MTHRF gene and risk of ALS in Polish population, the results of meta-analysis suggest that the TT genotype can be a genetic risk factor for ALS in Caucasian population.

ALS-FTD complex disorder due to C9ORF72 gene mutation – description of first Polish family

Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are complex neurodegenerative disorders that can be either sporadic or familial and can overlap clinically and pathologically. We present the first Central-Eastern European family with ALS-FTD syndrome due to a C9ORF72 repeat expansion. Methods: We studied a family consisting of 37 family members, 6 of whom were genetically evaluated for C9ORF72 expansions. Family members were evaluated clinically, by history, and by chart review. Results: Overall, 5 generations of the family were studied, and 6 affected family members were identified. All affected members were females and had a different clinical presentation, which was ALS, FTD or both. Among the genetically evaluated subjects, 5 carried a C9ORF72 expansion; 4 of these individuals remain clinically unaffected. Conclusion: Our report reveals that the hexanucleotide repeat expansion of C9ORF72, which is the most common genetic cause of ALS-FTD complex disorder, is also present in Central-Eastern Europe. Further studies are needed to assess the frequency of this expansion in the Polish population with familial as well as sporadic ALS, FTD and the ALS-FTD complex disorder.