Polimorfizm – 1562 C/T genu MMP-9 w chorobach naczyniowych mózgu w populacji polskiej

Background and purpose Matrix metalloproteinase 9 (MMP-9) is an endopeptidase degrading extracellular matrix. There is growing evidence that changes in extracellular matrix play an important role in vascular pathology, especially in cardiovascular and cerebrovascular disease. Previous studies have demonstrated that MMP-9 activity is controlled by –1562 C/T polymorphism. Genotypes with T allele (CT, TT) have higher enzymatic activity. Thus, this polymorphism could be responsible for the higher risk for cerebrovascular disease and death. The aim of this study was to assess the significance of MMP-9 polymorphism as a risk factor for cerebrovascular disease in a Polish population. Material and methods A total of 775 consecutive patients with a diagnosis of cerebrovascular disease (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage) admitted to the Stroke Unit, Jagiellonian University, Krakow, Poland between 2000 and 2004 were studied and compared with 766 matched controls. The polymorphism was studied by polymerase chain reaction (PCR) and restricted enzyme digestion. Results Among 418 patients with ischaemic stroke of various aetiologies and among 146 patients with primary intracerebral haemorrhage and 211 patients with subarachnoid haemorrhage due to ruptured intracranial aneurysm, statistical analysis did not show a significant difference between occurrence of CC, CT, TT genotypes or C and T alleles in patients with stroke of various aetiology compared with controls. Conclusions We found no association between the –1562 C/T MMP-9 polymorphism and ischaemic stroke, subarachnoid haemorrhage or spontaneous intracerebral haemorrhage in the studied Polish population.Wstęp i cel pracy Metaloproteinaza 9 (MMP-9) jest endo-peptydazą degradującą macierz zewnątrzkomórkową. Istnieje coraz więcej dowodów naukowych potwierdzających ważną rolę zmian w macierzy zewnątrzkomórkowej w chorobach naczyniowych, a szczególnie w chorobach serca i naczyń mózgowych. Badania dowiodły, że aktywność MMP-9 jest zależna od polimorfizmu –1562 C/T. Genotypy z allelem T (CT, TT) wykazują większą aktywność enzymatyczną, co może przyczyniać się do znaczenia tego polimorfizmu jako czynnika ryzyka chorób naczyniowych mózgu i śmierci. Celem tego badania była analiza związku wariantów polimorficznych genu MMP-9 z chorobami naczyniowymi mózgu w badanej populacji polskiej. Materiał i metody Badano łącznie 775 pacjentów przyjętych na Oddział Udarowy Kliniki Neurologii Uniwersytetu Jagiellońskiego w latach 2000–2004 z rozpoznaniem choroby naczyń mózgowych (tj. udaru niedokrwiennego, krwotoku śródmózgowego lub krwotoku podpajęczynówkowego) oraz 766 osób z grupy kontrolnej. Polimorfizm genu MMP-9 badano za pomocą techniki PCR i trawienia przy użyciu enzymu restrykcyjnego. Wyniki Analiza statystyczna nie wykazała istotnych różnic w występowaniu genotypów CC, CT i TT ani alleli C i T u 418 chorych na udar niedokrwienny o różnej etiologii, 146 osób z pierwotnym krwotokiem śródmózgowym ani u 211 chorych z krwotokiem podpajęczynówkowym z pękniętego tętniaka wewnątrzczaszkowego w porównaniu z osobami z grupy kontrolnej. Wnioski Nie odnaleziono związku polimorfizmu –1562 C/T genu MMP-9 z występowaniem udaru niedokrwiennego o różnej etiologii, krwotoku podpajęczynówkowego i pierwotnego krwotoku śródmózgowego w badanej populacji polskiej

Hypoglossal nerve palsy as an isolated syndrome of internal carotid artery dissection: A review of the literature and a case report

A review of literature on the dissection of internal carotid artery was presented with apresentation of a rare case of patient with transient left hypoglossal nerve palsy caused bymechanic compression from intramural hematoma in higher extracranial portion of dissected carotid artery confirmed in MRI and CT scans. The clinical presentation and management are discussed

Idiopatyczna czuciowa neuropatia trójdzielna. Opis przypadku

Idiopathic trigeminal sensory neuropathy is a rare clinical condition characterized by sensory disturbances on the face. Its symptoms may be permanent or temporary and a wide variety of diagnostic procedures is usually required to establish the diagnosis. Frequently, it is the first manifestation of a systemic disorder. In the majority of cases causal treatment is not possible, even though patients with trigeminal sensory neuropathy should be carefully monitored by physicians.Idiopatyczna czuciowa neuropatia trójdzielna to rzadka choroba dotycząca zaburzeń czucia w obrębie twarzy. Zjawisko to może mieć charakter przejściowy lub stały, diagnostyka zaś wymaga zazwyczaj wykonania wielu różnych badań. Często neuropatia trójdzielna jest pierwszym objawem choroby układowej. Najczęściej leczenie przyczynowe nie jest możliwe, jednak pacjenci z idiopatyczną neuropatią trójdzielną powinni być pod stałą opieką medyczną

Przypadek tzw. wariantu choroby Niemanna-Picka typu Ci omówienie propozycji terapeutycznych

Niemann-Pick disease type C is a rare hereditary disorder caused by mutation-disrupted metabolism of cholesterol and low-density lipoprotein (LDL). In most patients, symptoms begin in childhood with severe clinical progression. We present a patient with heterozygote mutations 3001A>G and 3019C>G with late onset of the disease and positive response to treatment with miglustat. Behaviour and educational problems in childhood were probably related to the disease diagnosed later.Choroba Niemanna-Picka typu C jest rzadkim schorzeniem dziedziczonym autosomalnie recesywnie, spowodowanym zaburzeniem metabolizmu i transportu cholesterolu i LDL. Zachorowanie w większości przypadków dotyczy okresu dziecięcego i ma ciężki przebieg kliniczny. W artykule przedstawiono przypadek pacjenta z potwierdzoną złożoną mutacją 3001A>G i 3019C>G o późnym początku wystąpienia zaburzeń neurologicznych i korzystną odpowiedzią na leczenie miglustatem. Zaburzenia zachowania w wieku dziecięcym i trudności w nauce są najprawdopodobniej związane przyczynowo z później zdiagnozowaną chorobą

Serum interleukin 15 levels in patients with seropositive myasthenia gravis do not correlate with disease severity

Aim To assess interleukin 15 (IL-15) serum levels in patients with seropositive myasthenia gravis (MG); searching for potential relationship between IL-15 levels and clinical features such as gender, age at onset, clinical presentation or treatment received. Background IL-15 plays pivotal role in T-cell dependent autoimmunity. Increased IL-15 serum levels have been reported in several autoimmune diseases including MG patients from Japan. Patients and methods Sera of 42 seropositive MG patients (66.7% women), mean age 50.6±23.7 years) have been tested by ELISA for IL-15 levels. Results There were no statistically significant differences between IL-15 serum levels in MG patients in comparison with controls as well as between subgroups of MG patients (early vs. late onset and thymoma MG). Mean/median IL-15 serum levels were similar in MG patients treated with corticosteroids (CS) and CS naïve. Outliers (very high values) were seen only in untreated generalized MG patients. Conclusions Serum interleukin 15 levels in patients with seropositive myasthenia gravis do not correlate with disease severity

Alpha-2-antiplasmin Arg407Lys polymorphism and cryptogenic ischemic cerebrovascular events: Association with neurological deficit

Objective Genetic background of cryptogenic ischemic stroke (IS) and transient ischemic attack (TIA) remains uncertain. Alpha-2-antiplasmin (α2AP) Arg407Lys polymorphism has been shown to be less common in patients with abdominal aortic aneurysm (AAA) compared with healthy controls. We investigated associations of α2AP Arg407Lys polymorphism with cryptogenic IS and TIA. Methods We studied 165 consecutive Caucasian patients who experienced cryptogenic IS (n=123) or TIA (n=42). Neurological outcomes were assessed using the modified Rankin Scale (mRS) in the acute phase of cerebral ischemia and 8 (6–12) months after the index episode. Patients were genotyped for α2AP Arg407Lys polymorphism (rs1057335) using real time PCR technique. Results The allele frequency of Arg407Lys polymorphism was: 0.82/0.18. The 407Lys allele was more frequent in TIA patients compared to the IS group (0.29 vs. 0.14, p=0.003). In the whole group, as well as in IS and TIA patients analyzed separately, possession of the 407Lys allele was associated with excellent outcome (mRS 0–1) during follow-up (p<0.05) but not in the acute phase of ischemic events both in thrombolyzed and nonthrombolyzed IS patients. The multivariate logistic regression model showed that the excellent outcome (mRS 0–1) assessed after 8 (6–12) months since the index cerebral ischemia was predicted by the occurrence of Lys407 allele (OR 6.18, 95% CI, 2.01–18.98, p=0.001). Conclusion The presence of 407Lys allele is associated with better prognosis in cryptogenic cerebrovascular events. Our findings suggest that the α2AP Arg407Lys polymorphism could be involved in the pathogenesis of cerebral ischemia and its outcomes

Does apoptosis occur in amyotrophic lateral sclerosis? TUNEL experience from human Amyotrophic Lateral Sclerosis (ALS) tissues

The role that apoptosis plays in the pathogenesis of amyotrophic lateral sclerosis (ALS) is still unclear. From our autopsy samples, we have undertaken an effort to verify if apoptosis in ALS really occurs or if can at least be detected. The study was performed using TUNEL method for screening the apoptotic changes in the autopsy samples from 8 ALS cases compared with 16 control cases. No features of apoptosis (DNA cleavages) were noted in any of the investigated regions of the central nervous system in ALS cases as well as in controls. These preliminary results seem to support the reports, which deny the role of apoptosis in human ALS. The following investigations using additional methods will be performed for detection the apoptotic signals in ALS

Mechanical thrombectomy in acute stroke – Five years of experience in Poland

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250±99min. 90.3% of the studied patients had MT within 6h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations

To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of >6 million single nucleotide polymorphisms (SNPs) in 532 LOMG cases (anti-acetylcholine receptor [AChR] antibody positive; onset age ≥50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations (rs4574025, P = 3.9 × 10−7, odds ratio [OR] 1.42) and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9 × 10−10, OR 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5 × 10−6, OR 1.62) encoding the PTPN22 R620W variant noted in early-onset myasthenia gravis (EOMG) and other autoimmune diseases. In contrast, EOMG-associated SNPs in TNIP1 showed no association in LOMG, nor did other loci suggested for EOMG. Many SNPs within the major histocompatibility complex (MHC) region showed strong associations in LOMG, but with smaller effect sizes than in EOMG (highest OR ∼2 versus ∼6 in EOMG). Moreover, the strongest associations were in opposite directions from EOMG, including an OR of 0.54 for DQA1*05:01 in LOMG (P = 5.9 × 10−12) versus 2.82 in EOMG (P = 3.86 × 10−45). Association and conditioning studies for the MHC region showed three distinct and largely independent association peaks for LOMG corresponding to (a) MHC class II (highest attenuation when conditioning on DQA1), (b) HLA-A and (c) MHC class III SNPs. Conditioning studies of human leukocyte antigen (HLA) amino acid residues also suggest potential functional correlates. Together, these findings emphasize the value of subgrouping myasthenia gravis patients for clinical and basic investigations and imply distinct predisposing mechanisms in LOMG