Lege Artis Medicinae

[Thrombotic thrombocytopenia after ChAdOx1 nCoV-19 vaccination]


JULY 13, 2021

Lege Artis Medicinae - 2021;31(07)



Further articles in this publication

Lege Artis Medicinae

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


[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. ]

Lege Artis Medicinae

[Neurological complications of COVID-19]


[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

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


[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

[Neuropsychiatric complications of COVID-19 infection]


[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

[Face mask associated dry eye syndrome during the COVID-19 pandemic]

SOHÁR Nicolette

[During the COVID-19 pandemic, the use of face mask was mandated to slow down also this way the spread of SARS-CoV-2. Dry eye syndrome is a multifactorial, common disease of the tear film and ocular surface, which has a significant negative effect on quality of life. The face mask and prolonged use of digital devices in home office and on-line school education raised the prevalence of dry eye syndrome among the patients. Eye irritation caused by the use of masks increased the risk of infection through the eye surface. This study concerns the effect of mask use on the eye surface during the COVID-19 pandemic, the prevention of this condition and its therapy options respectively.]

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Clinical Neuroscience

Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study

NÉMETH Klára Zsófia, SZÛCS Anna , VITRAI József , JUHÁSZ Dóra , NÉMETH Pál János , HOLLÓ András

We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients. This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine. Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05–1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27–3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16–0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding. Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

Clinical Neuroscience

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

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

Evaluation of the effectiveness of transforaminal epidural steroid injection in far lateral lumbar disc herniations

EVRAN Sevket, KATAR Salim

Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of pa­tient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.

Clinical Neuroscience

Electrophysiological investigation for autonomic dysfunction in patients with myasthenia gravis: A prospective study


Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.

Clinical Neuroscience

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]