Catatonia during COVID-19 pandemic - diagnostic and therapeutic approach.

Catatonia can be defined as an etiologically heterogeneous syndrome, with predominant psychomotor disturbances. Historically, the concept of catatonia has been associated with mental disorders, especially schizophrenia. However, nowadays our understanding of catatonia has evolved to recognize it as neuropsychiatric syndrome that can arise from diverse etiological factors ranging from neurological to systemic diseases. Furthermore, there is now a recognized association between catatonia and a broader spectrum of mental disorders. Catatonia as a secondary neuropsychiatric syndrome may be a clinical manifestation of COVID-19 also due to the known neuroinvasive potential of the SARS-CoV-2 virus or in connection with the overall somatic alteration of the patient. In clinical practice, co-infection with SARS-CoV-2 could impede the process of diagnosing and treating catatonia as the primary psychopathological syndrome. The administration of benzodiazepines and electroconvulsive therapy could endanger the patient's physical health with active COVID-19 infection. Management of catatonic syndrome associated with COVID-19 is a challenge and requires a comprehensive therapeutic approach. The article demonstrates the above-mentioned difficulties of treatment through two case presentations (Tab. 2, Ref. 29). Text in PDF www.elis.sk Keywords: catatonia, COVID-19, SARS-CoV-2, neuropsychiatry, diagnosis, differential.

Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice.

Agrin and its receptor MuSK are required for the formation of the postsynaptic apparatus at the neuromuscular junction (NMJ). In the current model the local deposition of agrin by the nerve and the resulting local activation of MuSK are responsible for creating and maintaining the postsynaptic apparatus including clusters of acetylcholine receptors (AChRs). Concomitantly, the release of acetylcholine (ACh) and the resulting depolarization disperses those postsynaptic structures that are not apposed by the nerve and thus not stabilized by agrin-MuSK signaling. Here we show that a miniaturized form of agrin, consisting of the laminin-binding and MuSK-activating domains, is sufficient to fully restore NMJs in agrin mutant mice when expressed by developing muscle. Although miniagrin is expressed uniformly throughout muscle fibers and induces ectopic AChR clusters, the size and the number of those AChR clusters contacted by the motor nerve increase during development. We provide experimental evidence that this is due to ACh, because the AChR agonist carbachol stabilizes AChR clusters in organotypic cultures of embryonic diaphragms. In summary, our results show that agrin function in NMJ development requires only two small domains, and that this function does not depend on the local deposition of agrin at synapses. Finally, they suggest a novel local function of ACh in stabilizing postsynaptic structures.

What mental health experts in Slovakia are learning from COVID-19 pandemic?

INTRODUCTION: The COVID-19 pandemic was confirmed to have spread to Slovakia on 6th March 2020. To date of paper submission, it has very favorable course. However, since the beginning healthcare workers have been working under increasing pressure, anxiety and fear. AIM: Authors evaluated the psychosocial impact of COVID-19 pandemic on mental health experts and their clinical practice in Slovakia. MATERIALS AND METHODS: A total of 157 mental health experts (79% women) submitted their responses via online questionnaire. RESULTS: The most frequent occupation categories were 38.2% outpatient psychiatrists, 26.1% inpatient psychiatrists and 20.4% psychologists. The mental health experts felt maximum of stress during the peak of Slovak COVID-19 crisis, which was identified as the situation just after the declaring the state of emergency by Slovak government. The main sources of stress were statistical data, prognoses and other public presented information. Mental health experts felt mainly personal stress, then general and working stress. They identified also pathological effect of COVID-19 pandemic on the mental status of their patients, especially with anxiety and affective disorders and advantages of use of telemedicine. CONCLUSION: Psychosocial support in Slovakia was newly organized in COVID-19 pandemic for medical professionals, patients and other inhabitants under high stress within a very short time. This unexpected situation has revealed to Slovakia the need for reform of the mental healthcare system.

Synapse loss in cortex of agrin-deficient mice after genetic rescue of perinatal death.

Agrin-deficient mice die at birth because of aberrant development of the neuromuscular junctions. Here, we examined the role of agrin at brain synapses. We show that agrin is associated with excitatory but not inhibitory synapses in the cerebral cortex. Most importantly, we examined the brains of agrin-deficient mice whose perinatal death was prevented by the selective expression of agrin in motor neurons. We find that the number of presynaptic and postsynaptic specializations is strongly reduced in the cortex of 5- to 7-week-old mice. Consistent with a reduction in the number of synapses, the frequency of miniature postsynaptic currents was greatly decreased. In accordance with the synaptic localization of agrin to excitatory synapses, changes in the frequency were only detected for excitatory but not inhibitory synapses. Moreover, we find that the muscle-specific receptor tyrosine kinase MuSK, which is known to be an essential component of agrin-induced signaling at the neuromuscular junction, is also localized to a subset of excitatory synapses. Finally, some components of the mitogen-activated protein (MAP) kinase pathway, which has been shown to be activated by agrin in cultured neurons, are deregulated in agrin-deficient mice. In summary, our results provide strong evidence that agrin plays an important role in the formation and/or the maintenance of excitatory synapses in the brain, and we provide evidence that this function involves MAP kinase signaling.

New insights into the roles of agrin.

The heparan sulphate proteoglycan agrin is expressed as several isoforms in various tissues. Agrin is best known as a crucial organizer of postsynaptic differentiation at the neuromuscular junction, but it has recently also been implicated in the formation of the immunological synapse, the organization of the cytoskeleton and the amelioration of function in diseased muscle. So the activities of agrin might be of broader significance than previously anticipated.