Neurodegeneration Dotaz Zobrazit nápovědu
Neurodegenerace s akumulací železa (NBIA – neurodegeneration with brain iron accumulation) představují heterogenní skupinu geneticky vázaných neurodegenerativních onemocnění charakterizovaných zvýšenou akumulací železa v bazálních gangliích s variabilním klinickým obrazem, ve kterém dominuje kombinace extrapyramidové symptomatiky s deteriorací kognitivních funkcí. Ve většině případů se jedná o onemocnění se začátkem v dětském věku, nicméně u některých typů jsou popisovány i adultní formy či formy s pozdním začátkem. V této práci uvádíme přehled recentních informací o jednotlivých typech NBIA s důrazem na jejich klinický a radiologický obraz. V závěru popisujeme případ pacientky se suspektní NBIA s pozdním začátkem.
Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of genetically-linked neurodegenerative diseases characterized by increased iron accumulation in the basal ganglia. They present with a combination of extrapyramidal symptoms with deterioration of cognitive functions. In most cases, they are diseases with onset in childhood, but adult-onset or late-onset forms are also described. In this paper, we present an overview of recent data on individual types of NBIA with an emphasis on clinical and radiologic findings. In conclusion, we describe a case of a patient with suspected late-onset NBIA.
- Klíčová slova
- beta-propeller protein-associated neurodegeneration (BPAN), fatty-acid hydroxylase-associated neurodegeneration (FAHN), COASY protein-associated neurodegeneration (CoPAN), Kufor-Rakeb syndrom (PARK 9), Woodhouse-Sakati syndrom, neuroferitinopatie, aceluroplazminémie,
- MeSH
- apoferritiny genetika MeSH
- dědičné degenerativní poruchy nervového systému * etiologie patofyziologie MeSH
- dystonie etiologie MeSH
- Hallervordenův-Spatzův syndrom * etiologie patofyziologie MeSH
- intracelulární signální peptidy a proteiny genetika MeSH
- kognitivní poruchy etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mutace MeSH
- neuroaxonální dystrofie * etiologie patofyziologie MeSH
- oxygenasy se smíšenou funkcí genetika MeSH
- transferasy genetika MeSH
- transportní proteiny genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
elektronický časopis
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurologie
- neurovědy
- NLK Publikační typ
- elektronické časopisy
The journal of nuclear medicine, ISSN 0161-5505 Vol. 63, Suppl. 1, june 2022
74 stran : ilustrace ; 28 cm
Neurodegenerácia asociovaná s pantotenátkinázou (PKAN) je zriedkavé autozomálne-recesívne hereditárne ochorenie charakterizované akumuláciou železa v mozgu. PKAN je fenotypovo klinicky rozmanité ochorenie, ktoré sa prejavuje v detskom veku aj v dospelosti. Typicky sa manifestuje poruchami reči a kombináciou motorických príznakov, ako dystónia a parkinsonizmus, postihnutie kortikospinálneho traktu, či retinopatia. Ochorenie býva tiež späté s neurobehaviorálnymi poruchami. Prezentujeme prípad 25-ročného muža s postupne progredujúcim trasom a neobratnosťou ľavej hornej končatiny, ktorých vzniku predchádzala porucha reči a úzkostné stavy. Klinicky boli u pacienta prítomné známky postihnutia extrapyramídového systému a kortikospinálneho traktu. MR mozgu zobrazilo v T 2 vážení ložiskové zmeny v globus pallidus typické pre PKAN (eye of the tiger sign). Molekulárno-geneticky sme u pacienta potvrdili mutáciu v géne pre pantotenátkinázu 2 (PANK2) v homozygotnom stave. Podrobné klinické vyšetrenie v spojení s neurozobrazovacími metódami pri neurodegeneratívnych syndrómoch asociovaných s hromadením železa vedie k správne zvolenej genetickej analýze.
Pantothenate kinase-associated neurodegeneration is a rare autosomal-recessive hereditary disorder that is characterized by accumulation of brain iron. PKAN has a diverse phenotypic expression with childhood or adult onset. It manifests typically with speech disturbances and combinations of motor symptoms such as dystonia, parkinsonism, corticospinal tract and/or retinopathy. This disorder is also associated with neurobehavioural changes. We present a case of a 25-year-old man with a speech defect and anxiety that proceeded to progressive tremor and clumsiness of the left upper extremity. Physical examination revealed signs of extrapyramidal dysfunction and corticospinal tract involvement. T2-weighted brain MRI images disclosed focal changes in the globus pallidus typical of PKAN in ("eye of the tiger sign"). Molecular genetic analysis confirmed the homozygous mutation in the gene for pantothenate-kinase 2 (PANK2). Detailed clinical examination associated with cranial imaging techniques results in appropriate genetic analysis.
- MeSH
- baklofen terapeutické užití MeSH
- botulotoxiny terapeutické užití MeSH
- cholinergní antagonisté terapeutické užití MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- farmakoterapie MeSH
- Hallervordenův-Spatzův syndrom diagnóza etiologie genetika MeSH
- klinický obraz nemoci MeSH
- kyselina pantothenová MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- metabolické nemoci mozku MeSH
- poruchy metabolismu železa MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments. OBJECTIVES: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. RESULTS: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. CONCLUSIONS: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- činnosti denního života MeSH
- dvojitá slepá metoda MeSH
- Hallervordenův-Spatzův syndrom * farmakoterapie genetika MeSH
- kyselina pantothenová analogy a deriváty MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Disruption of cerebral iron regulation appears to have a role in aging and in the pathogenesis of various neurodegenerative disorders. Possible unfavorable impacts of iron accumulation include reactive oxygen species generation, induction of ferroptosis, and acceleration of inflammatory changes. Whole-brain iron-sensitive magnetic resonance imaging (MRI) techniques allow the examination of macroscopic patterns of brain iron deposits in vivo, while modern analytical methods ex vivo enable the determination of metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes the whole brain, cellular, and subcellular patterns of iron accumulation in neurodegenerative diseases of genetic and sporadic origin. We also provide an update on mechanisms, biomarkers, and effects of brain iron accumulation in these disorders, focusing on recent publications. In Parkinson's disease, Friedreich's disease, and several disorders within the neurodegeneration with brain iron accumulation group, there is a focal siderosis, typically in regions with the most pronounced neuropathological changes. The second group of disorders including multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis shows iron accumulation in the globus pallidus, caudate, and putamen, and in specific cortical regions. Yet, other disorders such as aceruloplasminemia, neuroferritinopathy, or Wilson disease manifest with diffuse iron accumulation in the deep gray matter in a pattern comparable to or even more extensive than that observed during normal aging. On the microscopic level, brain iron deposits are present mostly in dystrophic microglia variably accompanied by iron-laden macrophages and in astrocytes, implicating a role of inflammatory changes and blood-brain barrier disturbance in iron accumulation. Options and potential benefits of iron reducing strategies in neurodegeneration are discussed. Future research investigating whether genetic predispositions play a role in brain Fe accumulation is necessary. If confirmed, the prevention of further brain Fe uptake in individuals at risk may be key for preventing neurodegenerative disorders.
414 s. : il.
- Konspekt
- Sociologie
- NLK Obory
- neurovědy
- zdravotně postižení
The purpose of this study was to investigate the content neurospecific markers protein S-100 and neuroenolaza in blood serum and tear fluid of patients with ocular ischemic syndrome. Material and methods. We observed 43 patients aged 57 to 79 years, mean age 67.3 ± 2.7 years. Control group consisted of 11 volunteers without ophthalmic symptoms. The main group consisted of 32 patients with OIS. The neurospecific proteins S100 and NSE were investigated in blood serum and tear fluid. Results. The study found that in patients of the control group the content of protein were within the normal range: S -100 in the tear fluid – 0,0662 ± 0,00335 mkg/l, in the blood serum 0,0508 ± 0,00241 mkg/l. In patients of the main group the indicators of protein in the tear fluid were elevated in all patients - 3,12 ± 0,246 mkg/l ( p<0.005). The normal evels in blood serum of marker S-100 was in 30 patients - 0,0589 ± 0,00303 mkg/l, while, in 2 patients protein S-100 were raised and averaged 0,2175±0,00725 mkg/l. It was found that in patients of the control group content of protein NSE in the tear fluid and blood serum were within normal values - 15,86 ± 0,148 Ng/ml, 15,60 ± 0,202 Ng/ml respectively. In the main group the amount of protein NSE tended to increase in the tear fluid in 23 patients and averaged 33,012 ± 3,2626 Ng/ml (p<0.005), a significant decrease the quantity of protein was observed in 9 patients, which amounted to 5,166 ± 0,8301 Ng/ml. At normal levels in the blood serum protein NSE detected in 30 patients and averaged 14,48 ± 0,263 Ng/ml, whereas, in 2 patients there was a significant increase of content of protein NSE and was 27,47 ± 3,068 Ng/ml. Conclusions. Thus, changes in the concentration of S100 and neuroenolaza in the tear fluid in patients with ocular ischemic European Medical, Health and Pharmaceutical Journal ISSN 1804-5804 syndrome allow to identify as marker of nerve cells damage of the eye, contributing to the definition in conjunction with other signs of stage and etiology of the disease.
- Klíčová slova
- oční ischemický syndrom,
- MeSH
- atrofie optického nervu diagnóza patofyziologie MeSH
- biologické markery * analýza krev MeSH
- fosfopyruváthydratasa analýza krev MeSH
- ischemie diagnóza patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- oční nemoci patologie MeSH
- proteiny S100 analýza krev MeSH
- senioři MeSH
- slzy chemie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
