Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.

• MeSH
• atrofie patologie   MeSH
• bílá hmota * diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• retrospektivní studie MeSH
• Tay-Sachsova nemoc * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Given the substantial dependence of neurons on continuous supply of energy, the distribution of major cerebral arteries opens a question whether the distance from the main supply arteries constitutes a modulating factor for the microstructural and functional properties of brain tissue. To tackle this question, multimodal MRI acquisitions of 102 healthy volunteers over the full adult age span were utilised. Relaxation along a fictitious field in the rotating frame of rank n = 4 (RAFF4), adiabatic T1ρ, T2ρ, and intracellular volume fraction (fICVF) derived from diffusion-weighted imaging were implemented to quantify microstructural (cellularity, myelin density, iron concentration) tissue characteristics and degree centrality and fractional amplitude of low-frequency fluctuations to probe for functional metrics. Inverse correlation of arterial distance with robust homogeneity was detected for T1ρ, T2ρ and RAFF4 for cortical grey matter and white matter, showing substantial complex microstructural differences between brain tissue close and farther from main arterial trunks. Albeit with wider variability, functional metrics pointed to increased connectivity and neuronal activity in areas farther from main arteries. Surprisingly, multiple of these microstructural and functional distance-based gradients diminished with higher age, pointing to uniformization of brain tissue with ageing. All in all, this pilot study provides a novel insight on brain regionalisation based on artery distance, which merits further investigation to validate its biological underpinnings.

• MeSH
• arterie MeSH
• bílá hmota * MeSH
• difuzní magnetická rezonance MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mozek MeSH
• pilotní projekty MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Our goal was to identify highly accurate empirical models for the prediction of the risk of febrile seizure (FS) and FS recurrence. In a prospective, three-arm, case-control study, we enrolled 162 children (age 25.8 ± 17.1 months old, 71 females). Participants formed one case group (patients with FS) and two control groups (febrile patients without seizures and healthy controls). The impact of blood iron status, peak body temperature, and participants' demographics on FS risk and recurrence was investigated with univariate and multivariate statistics. Serum iron concentration, iron saturation, and unsaturated iron-binding capacity differed between the three investigated groups (pFWE < 0.05). These serum analytes were key variables in the design of novel multivariate linear mixture models. The models classified FS risk with higher accuracy than univariate approaches. The designed bi-linear classifier achieved a sensitivity/specificity of 82%/89% and was closest to the gold-standard classifier. A multivariate model assessing FS recurrence provided a difference (pFWE < 0.05) with a separating sensitivity/specificity of 72%/69%. Iron deficiency, height percentile, and age were significant FS risk factors. In addition, height percentile and hemoglobin concentration were linked to FS recurrence. Novel multivariate models utilizing blood iron status and demographic variables predicted FS risk and recurrence among infants and young children with fever.

• MeSH
• deficit železa * MeSH
• febrilní křeče * diagnóza   etiologie   MeSH
• horečka komplikace   MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• studie případů a kontrol MeSH
• železo MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE Late onset Tay Sachs disease LOTS is a form of GM2 gangliosidosis an autosomal recessive neurodegenerative disorder characterized by slowly progressive cerebellar ataxia lower motor neuron disease and psychiatric impairment due to mutations in the HEXA gene The aim of our work was to identify the characteristic brain MRI findings in this presumably underdiagnosed disease METHODS

• MeSH
• atrofie MeSH
• dospělí MeSH
• gangliosidózy GM2 * MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nemoci mozečku * MeSH
• nemoci s pozdním začátkem MeSH
• onemocnění motorického neuronu * MeSH
• Tay-Sachsova nemoc * diagnostické zobrazování   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• amaurosis fugax diagnostické zobrazování   etiologie   MeSH
• embolie * MeSH
• lidé MeSH
• okluze retinální arterie * komplikace   diagnostické zobrazování   MeSH
• slepota MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• evokované potenciály * fyziologie   MeSH
• lidé MeSH
• motorické evokované potenciály fyziologie   MeSH
• neurologické manifestace MeSH
• neurologické vyšetření metody   MeSH
• sluchové evokované potenciály fyziologie   MeSH
• somatosenzorické evokované potenciály fyziologie   MeSH
• zrakové evokované potenciály fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Theoretical models of retinal hemodynamics showed the modulation of retinal pulsatile patterns (RPPs) by heart rate (HR), yet in-vivo validation and scientific merit of this biological process is lacking. Such evidence is critical for result interpretation, study design, and (patho-)physiological modeling of human biology spanning applications in various medical specialties. In retinal hemodynamic video-recordings, we characterize the morphology of RPPs and assess the impact of modulation by HR or other variables. Principal component analysis isolated two RPPs, i.e., spontaneous venous pulsation (SVP) and optic cup pulsation (OCP). Heart rate modulated SVP and OCP morphology (pFDR < 0.05); age modulated SVP morphology (pFDR < 0.05). In addition, age and HR demonstrated the effect on between-group differences. This knowledge greatly affects future study designs, analyses of between-group differences in RPPs, and biophysical models investigating relationships between RPPs, intracranial, intraocular pressures, and cardiovascular physiology.

• MeSH
• discus nervi optici * MeSH
• lidé MeSH
• nitrooční tlak MeSH
• pulzatilní průtok fyziologie   MeSH
• srdeční frekvence MeSH
• vena centralis retinae * fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Covid-19 způsobil posun směrem k technologiím orientovaným na spotřebitele, jako jsou mobilní zdravotní aplikace (mHealth). Většina aplikací mHealth však přístupný jazyk nepoužívá. Standardizované terminologie mají potenciál tento problém vyřešit, ale nebyly zjednodušeny pro spotřebitelské použití. Metodika: Použili jsme standardizovanou zdravotnickou terminologii, systém Omaha, jako rámec pro vývoj Simplified Omaha System Terms (SOST) pro použití v aplikaci mHealth, MyStrengths + MyHealth. Principy jednoduchého jazyka informovaly o vývoji SOST ve třech fázích, komunitní validační skupina umožnila zpětnou vazbu od různých koncových uživatelů, hodnocení čitelnosti poskytlo ověření požadované cílové úrovně čitelnosti. Výsledky: Věk členů v komunitní validační skupině (n = 19) byl v rozmezí od 22 do 74 let; 51 % muži, 84 % lidí jiné barvy pleti a 21 % vysokoškolsky vzdělaných. Úroveň čtení konečného SOST byla v průměru 3,86 na Coleman-Liau Index (čtvrtý stupeň). Případová studie ukázala, že v komunitní studii během pandemie covidu-19 byly vygenerovány smysluplné údaje o celkovém zdraví člověka. Závěr: Komunitní validace a hodnocení čitelnosti prokázaly přístupný jazyk pro klinickou terminologii. SOST byl úspěšně nasazen v MyStrengths + MyHealth a komunitní studii. Systém Omaha jako rámec pro SOST může umožnit integraci dat s klinickými datovými soubory. Budoucí výzkum by se měl zaměřit na validaci SOST v dalších jazycích a integraci v rámci platforem elektronického zdravotnictví.

Purpose: COVID-19 has caused a shift toward consumer-facing technology such as mobile health (mHealth) applications. However, most mHealth apps do not use accessible language. Standardized terminologies have potential to solve this problem but have not been simplified for consumer use. Methods: We used a standardized health terminology, the Omaha System, as the framework to develop the Simplified Omaha System Terms (SOST) for use within a mHealth application, MyStrengths + MyHealth. Plain language principles informed the SOST development in three phases, a community-validation focus group enabled feedback from diverse end-users, a readability assessment provide validation to the desired goal readability level. Results: The community-validation members (n = 19) ages ranged from 22 to 74; 51% male, 84% people of color, and 21% college educated. The reading level of the final SOST averaged 3.86 on the Coleman-Liau Index (fourth grade). A case study showed meaningful whole-person health data were generated in a community-led study during COVID-19. Conclusions: Community validation and readability assessment demonstrated accessible language for a clinical terminology. The SOST was deployed successfully in MyStrengths + My Health and in a community-led study. The Omaha System as a framework for the SOST may enable the data to be integrated with clinical datasets. Future research should focus on validation of SOST in additional languages and integration within electronic health platforms.

• Klíčová slova
• Omaha System,
• MeSH
• databáze jako téma MeSH
• informační systémy MeSH
• uživatelské rozhraní počítače MeSH

PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common drug-resistant epilepsy. Despite major advances in epilepsy research, the epileptogenesis of the MTLE-HS is not well understood. The altered neuroimmune response is one of the pathomechanisms linked to progressive epileptogenesis in MTLE-HS, and understanding its role may help design future cures for pharmaco-resistant MTLE-HS. Here, the neuroimmune function was evaluated by the assessment of cytokine-chemokine profiles in brain samples from the hippocampus of patients with MTLE-HS. METHODS: Brain samples from patients with MTLE-HS collected during epileptosurgical resection (n = 21) were compared to those obtained from autopsy controls (n = 13). The typing of HS was performed according to ILAE consensus classification, and patients were additionally sorted into subgroups based on the severity of neuronal depletion (Wyler grading system). Differences between patients with MTLE-HS with and without a history of febrile seizures were also assessed. RNA was isolated from native samples, and real-time gene expression analysis of cytokine-chemokine profiles, i.e., levels of IL-1β, IL-6, IL-10, IL-18, CCL2, CCL3, CCL4, and STAT3, was carried out by qRT-PCR methodology. RESULTS: Upregulation of IL-1β (p = 0.001), IL-18 (p = 0.0018), CCL2 (p = 0,0377), CCL3 (p < 0.001), and CCL4 (p < 0.001) in MTLE-HS patients was detected when compared to the post-mortem hippocampal samples collected from autopsy controls. The STAT3 expression was higher in more severe neuronal loss and glial scaring determined by different Wyler grades in HS patients. Furthermore, cytokine-chemokine profiles were not different in MTLE-HS patients with or without febrile seizures. CONCLUSION: The upregulation of specific cytokines and chemokines in MTLE-HS provides evidence that the neuroinflammatory process contributes to MTLE epileptogenesis. History of febrile seizures did not alter the immune profiles. Specific immune mediators and related immune pathways represent potential therapeutic targets for seizure control and pharmacoresistancy prevention in MTLE associated with hippocampal sclerosis.

• MeSH
• chemokiny metabolismus   MeSH
• cytokiny metabolismus   MeSH
• epilepsie temporálního laloku * komplikace   MeSH
• hipokampus patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• skleróza patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Despite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations. METHODS: Twenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls. RESULTS: Focal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T2 signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities. CONCLUSION: White matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T2 signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T2 signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.

• MeSH
• alfa-mannosidóza diagnóza   diagnostické zobrazování   patologie   MeSH
• atrofie diagnóza   diagnostické zobrazování   patologie   MeSH
• bílá hmota diagnostické zobrazování   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• malformace nervového systému diagnóza   diagnostické zobrazování   patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozeček diagnostické zobrazování   patologie   MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• neurozobrazování metody   MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH