Lege Artis Medicinae

[SARS Covid-19 as an immunothrombotic disease and the potential benefits of a new estrogen-free contraceptive containing drospirenone]

JAKAB Attila

JULY 13, 2021

Lege Artis Medicinae - 2021;31(07)

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Lege Artis Medicinae

[Neurological complications of COVID-19]

KOVÁCS Tibor, BERECZKI Dániel, LAMBERTUS Iván, DOBRONYI Levente

[The SARS-CoV-2 virus of COVID-19 is present in all countries of the world by 2021 causing primarily respiratory symptoms by penumonia with severe respiratory failure. Since the early stages of the pandemic, there were published case reports and comprehensive clinical studies about the neurological symptoms and complications of the infection (e.g. myalgia, anosmia, ageusia, encephalitis, encephalopathy, cerebrovascular conditions, Guillain-Barré syndrome and specific neuropathies). As it is well known, drugs used in therapeutic research may also have neurological adverse effects. Our summary aims to provide a practical overview of domestic and international literature about the already known neurological complications of SARS-CoV-2 infection.]

Lege Artis Medicinae

[Neuropsychiatric complications of COVID-19 infection]

FRECSKA Ede, BALLA Petra

[Initially, the studies of COVID-19 infection focused primarily on the acute and subacute somatic symptoms of limited duration, but later on with the spread of the pandemic the scope was extended to prolonged symptoms recognized as complications. Data are mounting about after-effects in circulation, respiration, coagulation, problematic outcomes in rheumatology, dermatology, ophthalmology, as well as about the acute and prolonged symptoms of the dysfunctional central nervous system. Initially, sporadic case reports, later results of population based studies and animal models were available, and the first systematic review articles were emerging during preparation of our survey. Lesions of the central nervous system may manifest themselves both in neurological symptoms and diseases or psychiatric complaints and syndromes. The scale of symptoms is broad, the pathomechanisms are not perfectly mapped thus all therapeutic approaches are in their infancy yet. Epidemiological data of neuropsychiatric complications are incomplete for the time being though they have been rapidly becoming more accurate. Conservative estimates assume tens of millions of people affected worldwide. More time is necessary to assess the persistence or improvement of the prolonged symptoms. Besides every efforts to block the spread of the virus, the utmost importance is to analyze the effects of the virus on the central nervous system and to develop effective treatment strategies. According to our current knowledge, the pathomechanism of neuropsychiatric complications is multifactorial. Beyond the direct deleterious effect of the virus on neuronal and glial functions, more important is that the serious consequences of cerebrovascular dysfunction and poor oxygenation have to be taken into consideration together with extended and prolonged systemic immunological processes, which markedly harm the brain tissue, notably neurons, axons, synapses and glia cells. Based on a non-systematic lite­ra­ture review our work details these me­chanisms and addresses therapeutic options as well. ]

Lege Artis Medicinae

[Potential benefits of using GLP1-receptor agonists during COVID-19 epidemic]

KIS János Tibor, SCHANDL László, GRÓSZ Andrea

[The risk of SARS-CoV-2 infection is higher among diabetic patients. The severity of progressing infection also increases in diabetes mellitus. Obesity associated with diabetes and cardiovascular disease are worsening the prognosis. Glucagon-like peptide-1 receptor agonists (GLP1-RA) administered in type 2 diabetes are lowering significantly the blood sugar level without increasing the risk of hypoglycaemia, support patients to lose weight, and reduce the likelihood of developing and worsening car­diovascular diseases. Through their many effects, they prepare diabetic patients to a certain extent to survive SARS-CoV-2 infection with fewer complications and have a beneficial immunological effect against the development of cytokine storm respectively. The authors summarize the potential beneficial effects of GLP1-RAs in SARS-CoV-2 infection.]

Lege Artis Medicinae

[Treatment options for localized and widespread post-COVID pain]

VERECKEI Edit

[Data on the new coronavirus caused di­s­ease and its treatment have been accumulating for more than a year. There are four main disease courses: no or mild symp­toms, unavoidable hospitalisation, severe or lethal outcome, and permanent or post-hoc manifestations. The last course is usually referred to as post-COVID syndrome. As a part of the acute and post-COVID symptomatology there were published pain perceptions with frequent but heterogeneous localisation. It is practical to classify them by the origin of pain: nociceptive/inflammatory, peripheral neuropathic or central. Additionally, we have to clear which phase is the post-COVID patient in i.e. the patient has the prolonged COVID- or persistent post-COVID syndrome. However, in addition to an acute general inflammatory reaction, a true inflammation of joints and muscles is very rare in the musculoskeletal system. The diffuse musculoskeletal pain, chronic fatigue, generalised anxiety and depressive disposition manifest themselves in both acute and persistent forms. Their explanation is essentially of neurological nature: there are para-infectious “neuro-inflammation”, i.e. neuropathic and central mechanisms in the background. Accor­ding­ly, therapeutic options must be chosen while concerning the neuropharmacological action mechanisms of analgesics. El­derly patients at high iatrogenic risk and with multiple co-morbidities may be treated transdermal instead of oral drug administration.]

Lege Artis Medicinae

[Mechanism of mucosal defence and options to reduce virus invasion during the COVID pandemic]

HODINKA László

[The portal of entry for coronavirus is the mucous membrane of the respiratory tract. Severity, organ manifestations and out­come of COVID-19 are determined by the viral load, burdening the attacked organism. Condition of the respiratory tract and gastrointestinal mucosa and the capacity of their defence system are crucial for virus penetration, fusion with epithelial cells and replication. Direct neural spread, penet­ra­tion into the deeper airways and spread through the lymph nodes depend on these functions. Virus binding and engulfment is an active process. The virus penetrates the endosomes of the epithelial cell, by enzymatic transfer where it is recognised by natural defence agents and triggers the first defence responses. These alarm the entire immune system and trigger a whole chain of inflammatory and enzymatic defence processes (cytokine and bradykinin storm) proportional to the viral load. The severity endpoint of COVID-19 pathology is alveolitis, cerebral vasculitis and intestinal da­mage, often with fatal outcome. The airway mucosa defends itself by secreting surface factors and recruiting and activating cells of the adaptive immune system. An important element of the latter is the early ap­pearance of secretory IgA in the mucosa. The viral invasion can be prevented by application of a nasal spray containing carrageenan, which engages the virus and prevents its attachment by the gel-forming property of carrageenan. This effect has worked in previous virus epidemics and the first COVID-19 experiences confirm its pro­tec­tive role. ]

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Cases of inborn errors of metabolism diagnosed in children with autism

CAKAR Emel Nafiye, YILMAZBAS Pınar

Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.

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Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

KISS Geza Jozsef, JARABIN András János, MOLNÁR Anna Fiona, KLIVÉNYI Péter, TISZLAVICZ László, GION Katalin, FÖLDESI Imre, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

Clinical Neuroscience

[The role of sleep in the relational memory processes ]

ZÁMBÓ Ágnes, PROKECZ Lídia, CSÁBI Eszter

[A growing body of evidence suggests that sleep plays an essential role in the consolidation of different memory systems, but less is known about the beneficial effect of sleep on relational memory processes and the recognition of emotional facial expressions, however, it is a fundamental cognitive skill in human everyday life. Thus, the study aims to investigate the effect of timing of learning and the role of sleep in relational memory processes. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. Our results suggest that the timing of learning and sleep plays an important role in the stabilizing process of memory representation to resist against forgetting.]

Lege Artis Medicinae

[COVID-19-cardiology at spring, 2020]

VÁLYI Péter