MuSK Myasthenia Gravis-Potential Pathomechanisms and Treatment Directed against Specific Targets.

Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies target structures within the neuromuscular junction, affecting neuromuscular transmission. Muscle-specific tyrosine kinase receptor-associated MG (MuSK-MG) is a rare, often more severe, subtype of the disease with different pathogenesis and specific clinical features. It is characterized by a more severe clinical course, more frequent complications, and often inadequate response to treatment. Here, we review the current state of knowledge about potential pathomechanisms of the MuSK-MG and their therapeutic implications as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of myasthenia gravis.

Future targets for migraine treatment beyond CGRP.

BACKGROUND: Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. FINDINGS: We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a PAC1 antibody have been tested for migraine treatment, albeit with ambiguous results. CONCLUSION: While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients.

COVID-19-related headache and innate immune response - a narrative review.

Headache is one of the most prevalent, although often underreported, symptoms of coronavirus disease 2019 (COVID-19). It is generally accepted that this symptom is a form of secondary headache due to systemic viral infection. There are several hypotheses that try to explain its aetiopathogenesis. One of the most compelling is related to innate immune response to viral infection. This rationale is supported by similarities to other viral infections and the temporal overlap between immunological reactions and headache. Moreover, several key factors in innate immunity have been shown to facilitate headache e.g. interferons, interleukin (IL) -1-ß, IL-6, and tumour necrosis factor. There is also a possibility that the virus causes headache by the direct activation of afferents through pattern recognition receptors (i.e. Toll-like receptor 7). Moreover, some data on post-COVID-19 headache and after vaccination against SARS-CoV-2 infection suggests a similar cytokine-mediated pathomechanism in these clinical situations. Future research should look for evidence of causality between particular immune response factors and headache. Identifying key molecules responsible for headache during acute viral infection would be an important step towards managing one of the most prevalent secondary headache disorders.

Cerebral Aneurysms Caused by Atrial Myxoma-A Systematic Review of the Literature.

Background: The association between cerebral aneurysms and left atrial myxoma is known but rare. We described its pathogenesis, clinical presentation, diagnostic findings and treatment using a systemic review of the literature. Methods: MEDLINE via PubMed was searched for articles published until August 2022 using the keywords "atrial myxoma", "cardiac myxoma" and "cerebral aneurysm". Results: In this review, 55 patients with multiple myxomas aneurysms were analyzed, and 65% were women. The average age when aneurysms were diagnosed was 42.5 ± 15.81; most patients were less than 60 years old (86%). Aneurysms could be found before the diagnosis, at the same time as cardiac myxoma, or even 25 years after resection of the atrial mass. In our review, the mean time to diagnoses was 4.5 years. Our review estimates that the most common symptoms were vascular incidents (25%) and seizures (14.3%). In 15 cases, variable headaches were reported. Regarding management strategies, 57% cases were managed conservatively as the primary choice. Conclusions: Although cerebral aneurysms caused by atrial myxoma are rare, the long-term consequences can be serious and patients should be monitored.

Tobacco and Nervous System Development and Function-New Findings 2015-2020.

Tobacco is a one of the most common addictive stimulants used by people around the world. The smoke generated during tobacco combustion is a toxic mixture of more than 5000 chemicals of which over 30 are known human carcinogens. While its negative effects on the human body are well understood, it remains a serious public health problem. One of the multiple effects of smoking is tobacco's effect on the nervous system-its development and function. This review aims to summarize the progress made in research on the effects of tobacco on the nervous system both of the perinatal period and adults and both in animals and humans in 2015-2020. The 1245 results that corresponded to the keywords "tobacco, cigarette, nervous system, brain, morphology, function" were reviewed, of which 200 abstracts were considered significant. Most of those articles broadened the knowledge about the negative effects of smoking on the human nervous system. Tobacco has a significant negative impact on the development of nervous structures, neurotransmission and cognitive functions, and promotes the development of neurodegenerative diseases, insomnia and cerebrovascular diseases. The only exception is the protective effect of the dopaminergic system in Parkinson's disease. In conclusion, in recent years much effort has been devoted to describing, revealing and uncovering new aspects of tobacco detrimental to human life. The nicotine contained in tobacco smoke affects the human body in a multidimensional way, including a serious impact on the broadly understood neurological health.

The Relationship between Occupationally Exposed Arsenic, Cadmium and Lead and Brain Bioelectrical Activity-A Visual and Brainstem Auditory Evoked Potentials Study.

The aim of this study was to evaluate the parameters of visual and brainstem auditory evoked potentials in patients occupationally exposed to arsenic, cadmium and lead. The study group comprised 41 copper smelter and refinery workers (average age: 51.27) with occupational exposure to arsenic, cadmium and lead. The control group consisted of 36 healthy volunteers (35 men and 1 woman, aged 27-66, average age: 51.08). Neurological examination, brain imaging, and visual and brainstem auditory evoked potentials were performed, and the relationship between blood Cd, Pb concentration (Cd-B, Pb-B), blood zinc protoporphyrin (ZnPP), and urine As concentration (As-U) were assessed. In the workers, exceedances of allowable biological concentrations were observed, with the urinary concentration of arsenic being 5.2%, the cadmium and lead in blood being 1.3%, while the case of ZnPP was 2.6%. The mean P100, relative P100, and N145 visual evoked potential (VEP) latencies were significantly longer in exposed workers than in the controls. The mean wave III and V brainstem auditory evoked potential (BAEP) latency and the mean wave III-V and I-V interpeak latencies were longer, and the I and V amplitude was lower in the workers than the controls. In summary, occupational exposure to As, Cd, and Pb is associated with prolonged latency and reduced evoked potential amplitude, but As-U, Pb-B, Cd-B, and ZnPP concentrations are not linearly related to potential components. The analysis of evoked potentials may be a useful method of assessment of the central nervous system in patients with occupational exposure to heavy metals.

Multiple fusiform cerebral aneurysms detected after atrial myxoma resection: a report of two cases.

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[Rare clinical form of glioblastoma multiforme]. / Rzadkie kliniczne odmiany glejaka wielopostaciowego.

Glioblastoma multiforme (glioblastoma multiforme - GBM) is the most malignant tumor classified by WHO. It is also the most common primary CNS tumor with a very aggressive course and unfavourable prognosis, usually develops in adults, and is typically located supratentorially in the fronto-temporal region. However, the literature describes an unusual position of GBM (e.g. spinal cord, pons, pineal region), familial gliomas unconnected with the family of gliomas predisposed to the occurrence of syndromes, unusual glioma and metastatic sites, gliomas transplanted with organs. In this paper, based on the available literature, the authors discuss an unusual and rare form of glioblastoma multiforme.