Ancient schwannoma of the cauda equina. / A cauda equina "ancient" típusú schwannomája.

Összefoglaló. A cauda equina daganatai a leggyakrabban lumbagós panaszokkal jelentkeznek. Általában késoi stádiumban ismerik fel oket, mivel lassan növekednek, az anatómiai környezet tágas, a megjeleno tünetek nem specifikusak, valamint az érintett betegek többsége fiatal és egyébként egészséges. Jelen közleményünkben egy ritka variáns, a cauda equinát érinto "ancient" típusú schwannoma esetének kórtörténetét és kezelését mutatjuk be. Mutéti ellátás során a daganat totális eltávolítása történt, ezt követoen a beteg panaszai megszuntek. Ezen daganat klinikai kimutatását preoperatív T1-, T2-súlyozott MRI tette lehetové, a pontos diagnózist azonban az eltávolított daganat patológiai szövettani feldolgozása biztosította. Irodalmi áttekintésünk alapján a cauda equinában ez a szövettani altípusú schwannoma kifejezetten ritka: nemzetközi szinten 3 ilyen publikált eset jelent meg, magyar nyelvu közlést a témában azonban nem találtunk. Orv Hetil. 2022; 163(5): 195-200. Summary. Tumors of the cauda equina generally present with lower back pain. They are usually recognized at a late stage as they grow slowly, the surrounding anatomical environment is spacious, the symptoms that appear are not specific, and the majority of the affected patients are young and otherwise healthy. In this paper, we present the diagnosis and treatment of a young male patient who has undergone the surgical removal of an ancient schwannoma of the cauda equina. During the operation, the tumor was completely resected, and following that the patient's complaints disappeared. The key point to an accurate diagnosis of this kind of tumor before the operation was the appropriate radiological study, i.e., T1-, T2-weighted MRI, and postoperatively the histological processing of the removed neoplasm. Reviewing the literature, this pathological type of schwannoma appeared to be extremely rare in the cauda equina: so far, only three cases have been published internationally, however, we could not find a single paper in the Hungarian medical literature on this topic. Orv Hetil. 2022; 163(5): 195-200.

Decreased Number of Mitochondria in Leukoaraiosis.

BACKGROUND AND AIMS: Leukoaraiosis (LA), one of the most frequent causes of an age-associated cognitive decline, can be associated with a poor quality of life, leading overall to far-reaching public health problems. Chronic hypoxia of the white matter of the brain may be a factor triggering this entity. LA may develop as a consequence of chronically insufficient cellular energy production and the accumulation of free radicals. METHODS: In this context, after hypothesizing that the number of healthy mitochondria can be crucial in this complex process, a case-control LA study was carried out in which we analyzed the numbers of deleted and non-deleted mitochondria (the common D-loop deletion) per white blood cell. A total of 234 patients with LA and 123 MRI alteration-free subjects served as a control group. RESULTS: Interestingly, it emerged that the ratio of deleted relative to non-deleted mitochondria is strongly associated with the risk of LA. The calculated K ratio in the LA group was significantly lower than the K ratio in the controls (LA: K 0.37 95% CI 0.05; controls: K 0.48, 95% CI 0.076, p < 0.001). CONCLUSIONS: Our study suggests that the ratio of the dmDNA and mDNA can be of great importance in the pathogenesis of LA.

A homozygous genetic variant of mitochondrial uncoupling protein 4 exerts protection against the occurrence of multiple sclerosis.

Multiple sclerosis (MS), which results in damage of the white matter at multiple foci, poses a far-reaching public health problem in view of the burden it imposes on the affected young and middle-aged. Some previous data suggested that roles could be played in the demyelinization of the white matter of the brain by the malfunctioning of the mitochondria and mitochondria-associated reactive oxygen species. In this context, we hypothesized that the finely tuned dynamic stability of the mitochondrial membrane potential (MMP), which is the main mirror of the functional state of the mitochondria, is essential for the intact nature of the glia cells in the brain. Setting out from this, our aim in this study was to examine how the rs10807344 and rs2270450 genetic variants of mitochondrial uncoupling protein 4 (mUCP4) can give rise to the development of MS, since mUCP4 is presumed to be of great importance in the regulation of the MMP and cellular energy metabolism. The clinical and genetic data on 120 relapsing-remitting MS patients and 250 neuroimaging alteration-free subjects were analyzed. The rs10807344 CC genotype proved to exert a protective effect against the occurrence of MS (neuroimaging alteration-free controls, 58%; MS group, 33%; P < 0.0000089; OR, 0.32; 95% CI: 0.2-0.56, P < 0.005). The present findings indirectly raise the possibility that a shift or imbalance in the finally regulated MMP plays a role in the development of MS.

Galectin-2 3279TT variant protects against the lymphotoxin-alpha 252GG genotype associated ischaemic stroke.

OBJECTIVE: The galectin-2 protein is presumed to play a regulatory role in the intracellular trafficking of the lymphotoxin-alpha (LTA) cytokine. LTA is a pro-inflammatory factor, its 252GG homozygote variant is considered as a susceptibility factor for arteriosclerosis and cardiovascular diseases. By contrast, the galectin-2-encoding gene LGALS2 3279TT homozygote variant has been demonstrated to exert protection against myocardial infarction by reducing the transcriptional level of galectin-2, thereby leading to a reduced extracellular secretion of LTA. METHODS: In the present study, we examined whether the LGALS2 3279TT homozygote variant alone can influence the prevalence of ischaemic stroke, and whether it can interact somehow with the disadvantageous LTA 252GG homozygote variant. Genetic and clinical data of 385 ischemic stroke patients and 303 stroke and neuroimaging alteration-free controls were analysed. RESULTS: The combination of the LGALS2 3279TT and LTA 252GG homozygote was significantly less frequent in the ischemic stroke group (1.56%) than in the controls (5.94%, p<0.00187; overall stroke group: crude OR: 0.25, 95% CI: 0.1-0.64; adjusted OR: 0.03, 95% CI: 0.025-0.71). CONCLUSIONS: This finding suggests a gene-gene interaction.

The combination of homozygous MTHFR 677T and angiotensin II type-1 receptor 1166C variants confers the risk of small-vessel-associated ischemic stroke.

Previous studies have suggested that both angiotensin II type-1 receptor (AT1R) 1166C and methylenetetrahydrofolate reductase (MTHFR) 677T variants can have disadvantageous effects on the small-vessel circulation under certain conditions. The purpose of this study was to analyze the possible consequences of the simultaneous distribution of these two genetic variants in different types of ischemic stroke. The genetic and clinical data on 357 ischemic stroke patients and 263 control subjects were analyzed by using univariate and logistic statistical approaches. Neither the MTHFR 677T nor the AT1R 1166C genetic variant alone conferred the risk of any subtype of ischemic stroke. The combination of the homozygous MTHFR 677TT genotype and at least one AT1R 1166C allele occurred more frequently in the ischemic stroke patients (8.68%) than in the controls (4.56%, p < 0.05). Specific subclassification of the patients revealed an accumulation of this combination in small-vessel-associated ischemic stroke (12.2%, p < 0.01); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.66 (95% confidence interval, 1.28-7.89; p < 0.05). These findings suggest that the combination of these two genetic factors can contribute to the development of small-vessel cerebral infarcts. Although the exact mechanism of action is not known, addition of the unfavourable effects on the endothelial function can be presumed.

Apolipoprotein A5 gene promoter region T-1131C polymorphism associates with elevated circulating triglyceride levels and confers susceptibility for development of ischemic stroke.

The possible pathogenic role of triglycerides (TG) in the development of ischemic stroke is still under extensive investigation. Recently, apolipoprotein (apo)A5 gene promoter region T-1131C polymorphism has been shown to associate with elevated serum TG levels. In the current work, a total of 302 subjects were classified as being large vessel-associated, small vessel-associated, or belonging to a mixed group of ischemic stroke-affected patients. The level of TG was increased in all groups (p < 0.01). The apoA5-1131C allele frequency was approximately twofold in all groups of stroke patients compared with the controls (5 vs 10-12%; p < 0.05); and the apoA5-1131C allele itself was also found to associate with increased TG levels in all groups. In a multivariate logistic regression analysis model adjusted for differences in age, gender, serum cholesterol, hypertension, presence of diabetes mellitus, smoking and drinking habits, and ischemic heart disease, a significantly increased risk of developing stroke disease was found in patients carrying the apoA5-1131C allele (p < 0.05; odds ratio OR = 2.1 [1.3-4.7]); this association was also proven for all subtypes of the stroke. The results presented here suggest that the apoA5-1131C allele is an independent risk factor for the development of stroke. Being that apoA5 gene is under the control of the peroxisome proliferator-activated receptor alpha, theoretically, the current observations also can have long-term therapeutic consequences.

Coexistence of angiotensin II type-1 receptor A1166C and angiotensin-converting enzyme D/D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke.

The renin-angiotensin system plays an important role in the maintenance of blood pressure homeostasis. The angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II. Angiotensin II, which binds the angiotensin II type-1 receptor (AT1R), is a potent vasoconstrictor. On a pathophysiological basis, both ACE I/D and AT1R A1166C polymorphism lead to an enhanced activity of the angiotensin II-AT1R axis, thereby possibly contributing to circulatory disturbances. A mutually facilitatory effect may be presumed between the two polymorphisms. We examined whether this synergistic effect is involved in the evolution of different types of ischemic stroke. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. Atotal of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. The ACE D allele combined with the AT1R 1166C allele did not yield a risk of ischemic stroke. However, the co-occurrence of the homozygous ACE D/D and at least one AT1R 1166C allele was more frequent in the ischemic stroke group than in the control group (22.4 vs 11%, p < 0.005, OR, 2.33; 95% CI, 1.46-3.7). After specific subgroup analysis, this synergistic association was even stronger for small-vessel ischemic stroke (OR, 3.44; 95% CI, 1.9-6.24; p < 0.0005). Multivariate logistic regression analysis of the data confirmed this association (adjusted OR, 3.54, 95% CI, 1.88-7.16; p < 0.0005). Our results demonstrate that ACE D/D and AT1R 1166C polymorphism were associated with the development of small-vessel ischemic stroke through a mutually facilitatory interplay between them. Genetic interactions might contribute to the altered functional network in renin-angiotensin system in vascular disorders.

Angiotensin II type-1 receptor A1166C polymorphism is associated with increased risk of ischemic stroke in hypertensive smokers.

Recent observations revealed a novel role of angiotensin-converting enzyme 2 and the angiotensin II type-1 receptor (AT1R) in lung injury, thereby extending knowledge about the functions of the angiotensin system. Angiotensin II, whose target is the AT1R, is a potent vasoconstrictor. Accordingly, an imbalance leading to enhanced activity of the angiotensin II-AT1R axis is postulated to contribute to both circulatory disturbances and lung injury. In this context, a functional single-nucleotide polymorphism, AT1R A1166C, which leads to enhanced responsiveness of the AT1R, has been postulated as a candidate susceptibility factor for ischemic stroke. The aim of our study was to investigate its occurrence in ischemic stroke and to analyze its possible synergistic associations with clinical risk factors. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. A total of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. Alone, the AT1R 1166C allele did not pose a risk of stroke. In hypertensive smokers, however, it was associated with an increased risk of ischemic stroke (OR 22.3, 95% CI 5.8-110.2, p<0.001). Further subgroup analysis revealed the same association for both small-vessel (OR 24.3, 95% CI 6.1-121.1, p<0.001) and large-vessel (OR 21.3, 95% CI 4.6-81.1, p<0.001) infarction. On a pathophysiological basis, our results suggest the possibility that the AT1R A1166C polymorphism might give rise to ischemic stroke indirectly via an unfavorable effect on the cardiorespiratory function.

Lymphotoxin-alpha gene 252G allelic variant is a risk factor for large-vessel-associated ischemic stroke.

A direct role of lymphotoxin-alpha (LTA) in promoting atherosclerotic plaque growth has been demonstrated recently. The different protein transcripts of the naturally occurring genetic variants of the LTA gene have been demonstrated to exhibit affected functions, and an allelic difference in binding to transcription factor(s) has also been suggested. The homozygous variant of LTA characterized by the intron 1 252A-->G (252G) transition, which naturally coexists with an exon 3 804C-->A (804A) single-nucleotide polymorphism (SNP), has been reported as a susceptibility gene for myocardial infarction. Because the atherosclerotic process is also an integral component in the pathogenesis of certain types of vascular stroke, we investigated the possible significance of the above SNPs in 353 ischemic stroke patients and 180 healthy controls. The homozygous LTA allele with the 252G and 804C SNPs occurred more frequently in stroke patients (13.9%) than in controls (7.20%, p<0.025). Specific subclassification of the patients revealed an accumulation of these SNPs in large-vessel, pathology-associated cerebral infarction (18.2%); multivariate logistic regression analysis of the data confirmed this association, with an odds ratio of 2.1 (95% confidence interval, 1.3-6.2; p<0.005). Elimination of all subjects with a history or evidence of ischemic heart disease, including myocardial infarction, did not affect this association. These data show that besides the role in the development of myocardial infarction, the homozygous carriage of the LTA allele with 252G and 804A SNPs is a novel susceptibility factor for largevesselassociated ischemic stroke.