Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a relatively rare inflammatory-associated neurometabolic complication. In this article, we present a case report of a 50-year-old male patient with a history of carbon monoxide poisoning. This acute poisoning, although successfully controlled during a stay in the intensive care unit of a local hospital, later led to persistent neurological symptoms. The patient was then treated in the inpatient unit of the rehabilitation clinic, where cognitive deterioration began to develop 20 days after admission. Subsequent examination using EEG and magnetic resonance imaging confirmed severe encephalopathy later complicated by SARS-CoV-2 infection with fatal consequences due to bronchopneumonia. Because currently there are no approved guidelines for the management of DEACMP, we briefly discuss the existing challenges for future studies, especially the application of rational immunosuppressive therapy already in the acute treatment phase of CO poisoning, which could prevent the development of a severe form of DEACMP.

• Klíčová slova
• CO poisoning, case study, delayed encephalopathy, glucocorticoids, neuroimaging,
• MeSH
• hospitalizace MeSH
• kognitivní poruchy * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nemoci mozku * diagnostické zobrazování   etiologie   MeSH
• otrava oxidem uhelnatým * komplikace   terapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The ALF transcription factor paralogs, AFF1, AFF2, AFF3, and AFF4, are components of the transcriptional super elongation complex that regulates expression of genes involved in neurogenesis and development. We describe an autosomal dominant disorder associated with de novo missense variants in the degron of AFF3, a nine amino acid sequence important for its binding to ubiquitin ligase, or with de novo deletions of this region. The sixteen affected individuals we identified, along with two previously reported individuals, present with a recognizable pattern of anomalies, which we named KINSSHIP syndrome (KI for horseshoe kidney, NS for Nievergelt/Savarirayan type of mesomelic dysplasia, S for seizures, H for hypertrichosis, I for intellectual disability, and P for pulmonary involvement), partially overlapping the AFF4-associated CHOPS syndrome. Whereas homozygous Aff3 knockout mice display skeletal anomalies, kidney defects, brain malformations, and neurological anomalies, knockin animals modeling one of the microdeletions and the most common of the missense variants identified in affected individuals presented with lower mesomelic limb deformities like KINSSHIP-affected individuals and early lethality, respectively. Overexpression of AFF3 in zebrafish resulted in body axis anomalies, providing some support for the pathological effect of increased amount of AFF3. The only partial phenotypic overlap of AFF3- and AFF4-associated syndromes and the previously published transcriptome analyses of ALF transcription factors suggest that these factors are not redundant and each contributes uniquely to proper development.

• Klíčová slova
• AFF3, AFF4, horseshoe kidney, intellectual disability, mesomelic dysplasia,
• MeSH
• dánio pruhované genetika   MeSH
• dítě MeSH
• epilepsie komplikace   genetika   MeSH
• fenotyp MeSH
• frekvence genu MeSH
• fúze ledvin genetika   MeSH
• jaderné proteiny chemie   nedostatek   genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mentální retardace genetika   MeSH
• missense mutace * MeSH
• mladiství MeSH
• mladý dospělý MeSH
• molekulární evoluce MeSH
• molekulární modely MeSH
• myši MeSH
• nemoci mozku etiologie   genetika   MeSH
• osteochondrodysplazie genetika   MeSH
• předškolní dítě MeSH
• sekvence aminokyselin MeSH
• stabilita proteinů MeSH
• syndrom MeSH
• transkripční elongační faktory chemie   genetika   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AFF3 protein, human MeSH Prohlížeč
• AFF4 protein, human MeSH Prohlížeč
• jaderné proteiny MeSH
• transkripční elongační faktory MeSH

The metabolism of sulfur-containing amino acids (SAAs) requires an orchestrated interplay among several dozen enzymes and transporters, and an adequate dietary intake of methionine (Met), cysteine (Cys), and B vitamins. Known human genetic disorders are due to defects in Met demethylation, homocysteine (Hcy) remethylation, or cobalamin and folate metabolism, in Hcy transsulfuration, and Cys and hydrogen sulfide (H2S) catabolism. These disorders may manifest between the newborn period and late adulthood by a combination of neuropsychiatric abnormalities, thromboembolism, megaloblastic anemia, hepatopathy, myopathy, and bone and connective tissue abnormalities. Biochemical features include metabolite deficiencies (e.g. Met, S-adenosylmethionine (AdoMet), intermediates in 1-carbon metabolism, Cys, or glutathione) and/or their accumulation (e.g. S-adenosylhomocysteine, Hcy, H2S, or sulfite). Treatment should be started as early as possible and may include a low-protein/low-Met diet with Cys-enriched amino acid supplements, pharmacological doses of B vitamins, betaine to stimulate Hcy remethylation, the provision of N-acetylcysteine or AdoMet, or experimental approaches such as liver transplantation or enzyme replacement therapy. In several disorders, patients are exposed to long-term markedly elevated Met concentrations. Although these conditions may inform on Met toxicity, interpretation is difficult due to the presence of additional metabolic changes. Two disorders seem to exhibit Met-associated toxicity in the brain. An increased risk of demyelination in patients with Met adenosyltransferase I/III (MATI/III) deficiency due to biallelic mutations in the MATIA gene has been attributed to very high blood Met concentrations (typically >800 μmol/L) and possibly also to decreased liver AdoMet synthesis. An excessively high Met concentration in some patients with cystathionine β-synthase deficiency has been associated with encephalopathy and brain edema, and direct toxicity of Met has been postulated. In summary, studies in patients with various disorders of SAA metabolism showed complex metabolic changes with distant cellular consequences, most of which are not attributable to direct Met toxicity.

• Klíčová slova
• S-adenosylhomocysteine hydrolase deficiency, adenosine kinase deficiency, cystathionine β-synthase deficiency, ethylmalonic encephalopathy, glycine N-methyltransferase deficiency, homocystinuria, methionine adenosyltransferase I/III deficiency, methionine restricted diet, remethylation defects, sulfite oxidase deficiency,
• MeSH
• aminokyseliny sírové metabolismus   MeSH
• cystein metabolismus   MeSH
• glutathion metabolismus   MeSH
• homocystein metabolismus   MeSH
• homocystinurie etiologie   metabolismus   MeSH
• játra metabolismus   MeSH
• lidé MeSH
• metabolické nemoci genetika   metabolismus   patologie   terapie   MeSH
• methionin metabolismus   MeSH
• methioninadenosyltransferasa metabolismus   MeSH
• metylace MeSH
• nemoci mozku etiologie   metabolismus   MeSH
• S-adenosylmethionin metabolismus   MeSH
• síra metabolismus   MeSH
• siřičitany metabolismus   MeSH
• sloučeniny síry metabolismus   MeSH
• sulfan metabolismus   MeSH
• vrozené poruchy metabolismu patologie   terapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny sírové MeSH
• cystein MeSH
• glutathion MeSH
• homocystein MeSH
• methionin MeSH
• methioninadenosyltransferasa MeSH
• S-adenosylmethionin MeSH
• síra MeSH
• siřičitany MeSH
• sloučeniny síry MeSH
• sulfan MeSH

Experimental studies in animals provide relevant knowledge about pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced injury can alter neuronal, glial cell population, brain vasculature and may lead to molecular, cellular and functional consequences. Regarding to its fundamental role in the formation of new memories, spatial navigation and adult neurogenesis, the majority of studies have focused on the hippocampus. Most recent findings in cranial radiotherapy revealed that hippocampal avoidance prevents radiation-induced cognitive impairment of patients with brain primary tumors and metastases. However, numerous preclinical studies have shown that this problem is more complex. Regarding the fact, that the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is highly important to investigate molecular, cellular and functional changes in different brain regions and their integration at clinically relevant doses and schedules. Here, we provide a literature review in order support the translation of preclinical findings to clinical practice and improve the physical and mental status of patients with brain tumors.

• MeSH
• centrální nervový systém patologie   účinky záření   MeSH
• ionizující záření MeSH
• kognitivní poruchy etiologie   patologie   MeSH
• lidé MeSH
• nádory mozku patologie   radioterapie   MeSH
• nemoci mozku etiologie   patologie   MeSH
• radiační poranění etiologie   patologie   MeSH
• sekundární malignity etiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The developmental and epileptic encephalopathies (DEEs) are heterogeneous disorders with a strong genetic contribution, but the underlying genetic etiology remains unknown in a significant proportion of individuals. To explore whether statistical support for genetic etiologies can be generated on the basis of phenotypic features, we analyzed whole-exome sequencing data and phenotypic similarities by using Human Phenotype Ontology (HPO) in 314 individuals with DEEs. We identified a de novo c.508C>T (p.Arg170Trp) variant in AP2M1 in two individuals with a phenotypic similarity that was higher than expected by chance (p = 0.003) and a phenotype related to epilepsy with myoclonic-atonic seizures. We subsequently found the same de novo variant in two individuals with neurodevelopmental disorders and generalized epilepsy in a cohort of 2,310 individuals who underwent diagnostic whole-exome sequencing. AP2M1 encodes the μ-subunit of the adaptor protein complex 2 (AP-2), which is involved in clathrin-mediated endocytosis (CME) and synaptic vesicle recycling. Modeling of protein dynamics indicated that the p.Arg170Trp variant impairs the conformational activation and thermodynamic entropy of the AP-2 complex. Functional complementation of both the μ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2μ conditional knockout mice revealed a significant impairment of CME of transferrin. In contrast, stability, expression levels, membrane recruitment, and localization were not impaired, suggesting a functional alteration of the AP-2 complex as the underlying disease mechanism. We establish a recurrent pathogenic variant in AP2M1 as a cause of DEEs with distinct phenotypic features, and we implicate dysfunction of the early steps of endocytosis as a disease mechanism in epilepsy.

• Klíčová slova
• Human Phenotype Ontology, clathrin-mediated endocytosis, computational phenotypes, developmental and epileptic encephalopathy, neurodevelopmental disorders, synaptic transmission,
• MeSH
• adaptorový proteinový komplex - mu-podjednotky genetika   MeSH
• adaptorový proteinový komplex 2 genetika   MeSH
• dítě MeSH
• endocytóza * MeSH
• epilepsie etiologie   patologie   MeSH
• klathrin genetika   metabolismus   MeSH
• kojenec MeSH
• lidé MeSH
• missense mutace * MeSH
• mladiství MeSH
• myši knockoutované MeSH
• myši MeSH
• nemoci mozku etiologie   patologie   MeSH
• neurovývojové poruchy etiologie   patologie   MeSH
• předškolní dítě MeSH
• sekvenování exomu MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adaptor protein complex 2, mu 2 subunit MeSH Prohlížeč
• adaptorový proteinový komplex - mu-podjednotky MeSH
• adaptorový proteinový komplex 2 MeSH
• klathrin MeSH

PURPOSE: To examine changes in the brain before liver transplantation caused by the accumulation of paramagnetic ion deposits and to investigate recovery after liver transplantation over a long-term horizon. MATERIALS AND METHODS: Fifteen patients indicated for liver transplantation, 26 patients up to 2 years after, and 40 patients 8-15 years after liver transplantation were subjected to MR relaxometry. T(1) and T(2) relaxation times in the basal ganglia, thalamus, and white matter were evaluated. RESULTS: Relaxometry revealed a shortening of the relaxation times due to the deposition of paramagnetic ions in the basal ganglia before liver transplantation (P < 0.05), complete normalization of the relaxation times shortly after transplantation in the globus pallidus and caudate nucleus, and partial recovery of T(2) in the putamen. Relaxation times remained stable even 15 years posttransplantation. Increased relaxation times posttransplantation were found in the white matter and thalamus. CONCLUSION: The shortening of the relaxation times observed in the basal ganglia before liver transplantation was caused by paramagnetic ion deposition. The recovery observable within 2 years after transplantation was permanent, and no recurrence of paramagnetic ion deposition was observed even 15 years posttransplantation. Changes in the white matter and thalamus after transplantation were attributed to damage caused by permanent exposure to immunosuppressants.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mozek patologie   MeSH
• nemoci mozku etiologie   patologie   MeSH
• transplantace jater škodlivé účinky   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Stressful life events cause a variety of conditions affecting cerebral and neuroendocrine functions. Repeated stressful events also may determine sensitization leading to an increase in responsiveness to stress stimuli. Recent findings suggest that cognitive and emotional dysregulation related to traumatic stress likely is linked to defective inhibitory functions that may also lead to temporo-limbic seizure-like activity, increased vulnerability to stressors, and dysregulated asymmetry in neural activity patterns that may influence interhemispheric dissociation. Together recent data show that dysregulation in the brain asymmetry and mental functioning may be caused by stress-related activation that can influence also the peripheral endocrine glands through the HPA axis and other pathways connecting the CNS and the target endocrine glands.

• MeSH
• dominance mozková fyziologie   MeSH
• funkční lateralita fyziologie   MeSH
• kindling fyziologie   MeSH
• lidé MeSH
• nemoci endokrinního systému etiologie   patofyziologie   MeSH
• nemoci mozku etiologie   patofyziologie   MeSH
• neurosekreční systémy patofyziologie   MeSH
• psychický stres komplikace   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• Hashimotova nemoc komplikace   MeSH
• lidé MeSH
• nemoci mozku etiologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH

Hashimoto's encephalopathy (HE) is a brain disease associated with autoimmune thyroid disease. Over 100 articles have been published on the topic, especially in connection with hypothyroidism. In addition to an overview of the relevant literature, we also report a case of a female patient with a rare association of HE with thyreotoxicosis. The patient presented with varied clinical-neurological symptoms: she had convulsions, psychotic symptoms, altered consciousness Examinations (laboratory tests, CT, MRI, EEG, CSL exams) detected increased level of proteins in the liquor, episodes of rhythmic delta activity on EEG, increased antithyreoidal antibody titre (TOOab, TGAb, TRAb) in serum. After initial treatment with carbimazole and hydrocortizone, the patient's condition dramatically improved and she was disconnected from artificial lung ventilation, conscious and convulsion-free. During the following 30 days, the patient would get worse after attempts to withdraw glucocorticoids. In spite of thyreotoxicosis, we classified the condition as HE and the patient was fully stabilised after pulse treatment with methylprednisolone. Clinically, the patient was subject to further outpatient follow up, without symptoms of encephalopathy; glucocorticoids were gradually withdrawn and were discontinued completely after another four months. The authors conclude that HE, even though rare, may pass unnoticed due to its symptoms which are similar to many other and more frequent diseases. HE should be considered in patients with potential or known autoimmune thyroidism and atypical neuropsychiatric manifestation responding to corticoid treatment.

• MeSH
• dospělí MeSH
• Hashimotova nemoc komplikace   MeSH
• lidé MeSH
• nemoci mozku diagnóza   etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH

• MeSH
• Hashimotova nemoc komplikace   imunologie   MeSH
• lidé MeSH
• nemoci mozku diagnóza   etiologie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH