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Clinical Neuroscience

MARCH 30, 2016

Cerebral amyloid angiopathy related inflammation: is susceptibility weighted imaging the clue for diagnosis?

CSÉCSEI Péter, KOMOLY Sámuel, SZAPÁRY László, BARSI Péter

Background - Cerebral amyloid angiopathy-related inflammation (CAA-ri) is characterized by various neurological symptoms such as gradually developing confusion, progressive cognitive decline, seizure or headaches; T2 hyperintensities on magnetic resonance imaging (MRI); and neuropathological evidence of cerebral amyloid angiopathy (CAA) and associated vascular or perivascular inflammation. Although histological confirmation is necessary for accurate diagnosis, in case of typical clinical features and neuroimaging, the diagnosis can be established without biopsy. Case summary - We present the case of a 57-year-old man with a history of hypertension who presented to the emer¬gency department 3-week history of progressive headache and a gradually developing altered mental status. On examination, he was found to have left sided weakness and decreased pscyhomotility. Routine clinical work-up (lab investigations, CT, cerebrospinal fluid analysis) did not show obvious diagnosis, so we performed an MRI. It raised the suspicion of CAA-ri which diagnosis was verified by neuroradiological evaluation. High dose steroid treatment was initiated. The patient rapidly responded to treatment, his focal neurological signs resolved. Control MRI after 1.5 months showed multiple haemorrhagic laesions in the field of previous inflammation which posteriorly supported the previous supposed work-diagnosis. Conclusions - Although histopathology is the gold standard for the diagnosis of cerebral amyloid angiopathy, the typical clinical presentation, good response to steroids and accurate neuroradiological criteria make biopsy unnecessary to diagnose CAA-ri.

Clinical Neuroscience

JANUARY 30, 2016

Long term follow-up of lesional and non-lesional patients with electrical status epilepticus in slow wave sleep

HEGYI Márta, SIEGLER Zsuzsa, FOGARASI András, BARSI Péter, HALÁSZ Péter

Objectives – A retrospective study has been done at the Bethesda Children’s Hospital Epilepsy Center with those patients whose EEG records fulfilled in one or more records the criteria of electrical status epilepticus in slow wave sleep (ESES) pattern, occupying at least 75% of NREM sleep with bilateral discharges, and had detailed disease history and long term follow-up data, between 2000 and 2012. Patients and methods – Thirty-three patients (mean 11.1±4.2 years of age) were studied by 171 sleep EEG records. Sleep was recorded after sleep deprivation or during spontaneous sleep at least for one hour length of NREM. From the 492 EEGs, 171 sleep records were performed (average five/patient). Average follow-up time was 7.5 years. Eighty-two ESES records have been analyzed in 15 non-lesional and 18 lesional (11 with dysgenetic and seven with perinatal - asphyxic or vascular origin) patients. Variability of seizure types, seizure frequency and frequency of status epilepticus was higher in the lesional group. Impairment of the cognitive functions was moderate and partial in the non-lesional, while severely damaged in the lesional group. Results – EEG records of 29 patients showed unihemispherial spike fields with a perpendicular axis (in anterior, medial and posterior variants) to the Sylvian fissure, regardless their lesional or non-lesional origin. Only three (1one non-lesional and two lesional) patients had bilateral synchronous spike-wave discharges with bilateral symmetric frontocentral spike fields. The individual discharges of the sleep EEG pattern were very similar to the awake interictal records except their extension in time and field, their increased number, amplitude, and continuity of them and furthermore in the increased trans-hemispheral propagation and their synchronity. Conclusions – Assumed circuits involved in the pathomechanism of discharges during NREM sleep in ESES are discussed based on our findings.

Clinical Neuroscience

JANUARY 30, 2016

To treat or not to treat, cheyne-stokes respiration in a young adult with vascular encephalopathy

HUBATSCH Mihaela, ENGLERT Harald, WAGNER Ulrich

Cheyne-Stokes respiration (CSR) is a form of sleep-disordered breathing characterised by recurrent central sleep apnoea alternating with a crescendo-decrescendo pattern of tidal volume, relatively rare observation in sleep labs. It is mainly seen in severe heart failure and stroke. We report the case of a young man with CSR after sudden onset of seizure in the context of hypertensive exacerbation leading to the diagnosis of a leukoencephalopathy, and comment on differential diagnoses, prognostic and therapeutic outcomes. The very uniqueness of this case consists in the extremely young age for developing a vascular encephalopathy in the absence of genetic diseases and without previous diagnose of hypertension. There is no adequate explanation for the origin of vascular encephalopathy; also there is lack of evidence regarding the benefits and modality of treatment for CSR in neurologic diseases. Thus, we were forced to find the best compromise in a nocturnal oxygen therapy and follow-up.

Hypertension and nephrology

APRIL 24, 2020

[Arterial hypertension and atrial fibrillation - the most important risk factors for stroke in clinical practice ]

LUDOVIT Gaspar, VESTENICKA Veronika, CAPRNDA Martin

[Vascular stroke is a very frequent cause of morbidity and mortality, and in patients who suffered stroke subsequent long-term neurological deficit of greater or lesser extent is an important factor. Numerous clinical and epidemiological studies confirmed that elevated systemic blood pressure is among the main risk factors of both ischemic and hemorrhagic vascular stroke, the effects of arterial hypertension being very complex including morphological and functional changes in vessels and vascular circulation. In our retrospective analysis of 218 patients hospitalized for stroke we found arterial hypertension in 91.2% of subjects and atrial fibrillation in 32.1% of subjects. 182 patients (83.5%) have been diagnosed with ischemic stroke and 36 patients (16.5%) with hemorrhagic stroke. In the group of patients with atrial fibrillation, only 33 patients (47.1%) were treated by anticoagulants, what points out an inadequate indication of anticoagulant treatment when considering the stroke risk calculation for atrial fibrillation (CHA2DS2- VASc Score) and bleeding risk (HAS-BLED Calculator for Atrial Fibrillation). It is also noteworthy that in the group of patients with anticoagulant therapy who have developed ischemic stroke in spite of this treatment, we found that in 48.5% the treatment was underdosed and therefore ineffective. Our work points to the need to improve the effective management of arterial hypertension and atrial fibrillation, the most common modifiable factors of vascular strokes.]

Hypertension and nephrology

APRIL 24, 2020

[Cardiovascular risk assessment in chronic kidney disease, significance of left ventricular myocardial mass index]

SÁGI Balázs, KÉSŐI István, VAS Tibor, CSIKY Botond, NAGY Judit, KOVÁCS Tibor

[Introduction: Earlier studies have shown that cardiovascular (CV) mortality and morbidity in chronic kidney disease (CKD) often exceed their average population, and left ventricular hypertrophy (LVH) is an independent risk factor for CV disease. However, in CKD, the relationship between LVH, arterial stiffness (AS) and renal function has not yet been fully elucidated. Little data is available on their prognostic role. Aims of our study a) cross-sectional examination of the relationship between left ventricular mass index (LVMI), arterial vascular stiffness, and renal function, b) in our follow-up study, clarification of the LVMI, the prognostic role of AS in patients with CKD, IgA nephropathy (IgAN). Methods: In our cross-sectional study, 79 IgAN patients were examined in our clinic. The myocardial mass index (LVMI) was determined using an estimation formula after echocardiographic measurements. Arterial stiffness was measured using a photoplethizmography technique (PulseTrace) and characterized by the stiffness index (SI). The MDRD formula was used to estimate renal function (GFR) (eGFR, ml/min/1.73 m2). In the prognostic study the primary combined endpoint was total mortality, the most important CV events (stroke, myocardial infarction or cardiovascular interventions such as revascularization) and end stage renal disease. Secondary endpoints were CV and renal endpoints separately. Results: Of the 79 patients included in our cross-sectional study, 50 were men, with an average age of 46 ± 11 years. The mean value of LVMI was 106.66 ± 22.98 g/m2. Patients were divided into groups of 115 g/m2 for males considered to be abnormal and 95 g/m2 for women. LVMI is closely correlated with SI and inversely with eGFR (corr. coeff: 0.358; p <0.05 or -0.526; p <0.001). In case of LVH, SI was significantly higher in both sexes (p = 0.005 in males, p = 0.04 in females). In case of higher LVMI, renal function was significantly lower (p = 0.002 in males, p = 0.01 in females). Metabolic syndrome occurred in several cases in both sexes with LVH, but the difference was only significant in male patients (males 6 vs. 10, p = 0.008; females 2 vs. 4, p = 0.29). In our follow-up study, the presence of LVH in men significantly reduced survival in both primary and secondary endpoints, whereas in women there was no significant difference. Conclusion: In IgAN decreasing of renal function is closely related to left ventricular hypertrophy and vascular stiffness, as well as a close relationship was found between LVMI and AS. Reduced renal function is associated with an increase in LVMI and an increase in AS, which may result in a worse prognosis for both CV and renal outcomes. The underlying role of all these can be assumed to be a common vascular and myocardial pathological remodeling.]

Clinical Oncology

APRIL 10, 2019

[CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions]

SPRING M. Laura, WANDER A. Seth, ZANGARDI Mark, BARDIA Aditya

[Purpose of review: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+MBC) as well as current controversies and evolving areas of research. Recent fi ndings: Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the fi eld include whether all patients with HR+MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. Summary: The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.]

Clinical Oncology

FEBRUARY 20, 2019

[Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer]

RODRIGO Dienstmann, RAMON Salazar, JOSEP Tabernero

[Colorectal cancer (CRC) has clinically-relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations defi ne a population refractory to EGFR monoclonal antibodies, BRAFV600E mutations associate with poor outcome under standard therapies and response to targeted inhibitors in combinations, while HER2 amplifi cations confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to EGFR monoclonal antibodies have been described with signifi cant overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential predictive value in metastatic CRC. These markers refl ect stromal and immune microenvironment interactions with cancer cells. For example, the microsatellite instable (MSI) or POLE ultramutant CRC population is particularly sensitive to immune checkpoint inhibitors, while tumors with a mesenchymal phenotype are characterized by activation of immunosuppressive molecules that mandate stratifi ed development of novel immunotherapy combinations. In this manuscript we review the expanding landscape of targetable oncogenic alterations and signatures in metastatic CRC and discuss the clinical implementation of novel molecular diagnostic tests.]

Clinical Oncology

DECEMBER 10, 2018

[Advancing therapies in metastatic castration-resistant prostate cancer]

GIULIA Baciarello, MARCO Gicci, KARIM Fizazi

[Introduction: Prostate cancer is the second most common cause of cancer world wide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the corner stone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatment shaved ramatically improved overall survival of men with mCRPC. Current therapies are basedon AR-axis inhibitors and taxane-based chemotherapies, aswell as radiopharmaceuticals and Sipuleucel T. Areas covered: The authors provide a review of the current fi eld of systemic therapy in metastatic CRPC. This is followed by an in-depth analysis of recent developments in treatment, and the biological rationale behind these therapies. Expert opinion: Since several trials with docetaxel or novel hormonal agents showed improvement in overall survival in metastatic castration-sensitive prostate cancer, aswell as in non-metastatic castrationresistant patients, it is expected that a growing subgroup of patients will be expose dearlierto chemotherapy and to AR targeted agents. It becomes then fundamental to fi nd novel strategies to over come drug resistance and further improve survival.]

Hypertension and nephrology

DECEMBER 12, 2019

[Hypertension and brain function. Correlation of high blood pressure and demencia in aging. Hypertension in young-middle adults - demencia in elderly]

SZÉKÁCS Béla, KÉKES Ede

[The cerebral vascular damage caused by hypertension is manifested primarily in cognitive dysfunction, which is caused by hypoperfusion of brain tissue, ischemic, or bleeding stroke, or white matte injury. Hypertension may not only result in cerebral damage to the vascular background - dementia -, but may also contribute to the development and progression of classical gene-related Alzheimer’s disease. Blood pressure gradually increases in the elderly and in the very elderly, and the frequency of hypertension-mostly as isolated systolic hypertension - is 50% to 70%. High blood pressure predominately, or in full, means not only an increase in the circulatory resistance of the small children, but also, as part of the aging of the body, the rigidity (stiffness) of the arteries. At the same time, the incidence of dementia, along with age, rises sharply - up to 20% in those over 65 years of age, and over 40% in 80-90 years of age. The relationship between high blood pressure and dementia from the young age to the very old age may change as a function of current age. In the very old age of life, the varying influence of other pathological factors other than hypertension is becoming more and more important in the deterioration of both the vascular structure and the brain function. In this late stage of life, the very advanced rate of aging and nutritive blood flow often require higher perfusion pressure, and the not enough thought-out blood pressure reduction can be more damaging than a protective effect on brain condition or function. SPRINT MIND - the Intense Blood Pressure Reduction - hasn’t resolved the question, and we can legally assume that the 130-140 Hgmm SBP. Is the most favorable for dementia. The value of DBP 70 Hgmm is definitely unfavorable.]

Lege Artis Medicinae

DECEMBER 10, 2019

[Praeeclampsia - 2019]

TAMÁS Péter, KOPPÁN Miklós

[Preeclampsia remains one of the most serious gestational diseases. Accumulating data support the opinion that the pathogenesis of preeclampsia (gestational hypertension + organ dysfunction) is not homogenous. The early-onset (onset of clinical phase before the 34th gestational week) type is a placental disease in which hypertension and organ dysfunctions are due to vasoconstriction and microthrombosis. The late-onset form is a maternal disease in which water retention - in connection with obesity - beyond the given vascular capacity may be an important progenitor of the clinical signs. These considerations should also influence the strategy of the treatment. ]