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1.
J Neurosci ; 44(31)2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-38969506

RESUMEN

Although hyperactivity is associated with a wide variety of neurodevelopmental disorders, the early embryonic origins of locomotion have hindered investigation of pathogenesis of these debilitating behaviors. The earliest motor output in vertebrate animals is generated by clusters of early-born motor neurons (MNs) that occupy distinct regions of the spinal cord, innervating stereotyped muscle groups. Gap junction electrical synapses drive early spontaneous behavior in zebrafish, prior to the emergence of chemical neurotransmitter networks. We use a genetic model of hyperactivity to gain critical insight into the consequences of errors in motor circuit formation and function, finding that Fragile X syndrome model mutant zebrafish are hyperexcitable from the earliest phases of spontaneous behavior, show altered sensitivity to blockade of electrical gap junctions, and have increased expression of the gap junction protein Connexin 34/35. We further show that this hyperexcitable behavior can be rescued by pharmacological inhibition of electrical synapses. We also use functional imaging to examine MN and interneuron (IN) activity in early embryogenesis, finding genetic disruption of electrical gap junctions uncouples activity between mnx1 + MNs and INs. Taken together, our work highlights the importance of electrical synapses in motor development and suggests that the origins of hyperactivity in neurodevelopmental disorders may be established during the initial formation of locomotive circuits.


Asunto(s)
Sinapsis Eléctricas , Síndrome del Cromosoma X Frágil , Neuronas Motoras , Proteínas de Pez Cebra , Pez Cebra , Animales , Síndrome del Cromosoma X Frágil/fisiopatología , Síndrome del Cromosoma X Frágil/genética , Sinapsis Eléctricas/fisiología , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Neuronas Motoras/fisiología , Modelos Animales de Enfermedad , Conexinas/genética , Conexinas/metabolismo , Animales Modificados Genéticamente , Hipercinesia/fisiopatología , Interneuronas/fisiología , Interneuronas/metabolismo , Uniones Comunicantes/efectos de los fármacos , Uniones Comunicantes/metabolismo , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo
2.
Neurotoxicol Teratol ; 104: 107373, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39025421

RESUMEN

Non-coplanar polychlorinated biphenyl (PCB) mixture Aroclor 1254 and polybrominated diphenyl ether (PBDE) BDE-47 are known to impede neurogenesis and neuronal development. We previously reported that exposure to PCB and PBDE leads to increased embryonic movement in zebrafish by decreasing dopamine levels. In this study, we studied the connection between the melanin and dopamine synthesis pathways in this context. Both genetic and chemical inhibition of tyrosinase, the rate-limiting enzyme in melanin synthesis, not only led to reduced pigmentation but also inhibit PCB/PBDE-induced embryonic hyperactivity. Furthermore, PCB and PBDE rarely affected tyrosinase expression in the potential pigment cells, suggesting that these compounds reduce dopamine through enzymatic regulation, including a competitive interaction for the substrate tyrosine. Our results provide new insights into the interactions between melanogenesis and dopaminergic neuronal activity, which may contribute to understanding the mechanisms underlying PCB/PBDE toxicity in developing organisms.


Asunto(s)
Éteres Difenilos Halogenados , Monofenol Monooxigenasa , Bifenilos Policlorados , Pez Cebra , Animales , Monofenol Monooxigenasa/metabolismo , Éteres Difenilos Halogenados/toxicidad , Bifenilos Policlorados/toxicidad , Melaninas/metabolismo , Melaninas/biosíntesis , Pigmentación/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Hipercinesia/inducido químicamente , Dopamina/metabolismo , Conducta Animal/efectos de los fármacos
3.
Biochem Biophys Res Commun ; 729: 150361, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38972141

RESUMEN

Carnosine, anserine, and homocarnosine are histidine-containing dipeptides (HCDs) abundant in the skeletal muscle and nervous system in mammals. To date, studies have extensively demonstrated effects of carnosine and anserine, the predominant muscular HCDs, on muscular functions and exercise performance. However, homocarnosine, the predominant brain HCD, is underexplored. Moreover, roles of homocarnosine and its related HCDs in the brain and behaviors remain poorly understood. Here, we investigated potential roles of endogenous brain homocarnosine and its related HCDs in behaviors by using carnosine synthase-1-deficient (Carns1-/-) mice. We found that old Carns1-/- mice (female 12 months old) exhibited hyperactivity- and depression-like behaviors with higher plasma corticosterone levels on light-dark transition and forced swimming tests, but had no defects in spontaneous locomotor activity, repetitive behavior, olfactory functions, and learning and memory abilities, as compared with their age-matched wild-type (WT) mice. We confirmed that homocarnosine and its related HCDs were deficient across brain areas of Carns1-/- mice. Homocarnosine deficiency exhibited small effects on its constituent γ-aminobutyric acid (GABA) in the brain, in which GABA levels in hypothalamus and olfactory bulb were higher in Carns1-/- mice than in WT mice. In WT mice, homocarnosine and GABA were highly present in hypothalamus, thalamus, and olfactory bulb, and their brain levels did not decrease in old mice when compared with younger mice (3 months old). Our present findings provide new insights into roles of homocarnosine and its related HCDs in behaviors and neurological disorders.


Asunto(s)
Conducta Animal , Depresión , Dipéptidos , Animales , Femenino , Dipéptidos/metabolismo , Ratones , Depresión/metabolismo , Depresión/genética , Encéfalo/metabolismo , Carnosina/análogos & derivados , Carnosina/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Hipercinesia/metabolismo , Hipercinesia/genética , Envejecimiento/metabolismo , Histidina/análogos & derivados , Histidina/metabolismo , Histidina/deficiencia
4.
Ann Afr Med ; 23(3): 512-513, 2024 Jul 01.
Artículo en Francés, Inglés | MEDLINE | ID: mdl-39034583

RESUMEN

Hyperkinesias in a patient with complex-I deficiency due to the variant m.10191T>C in MT-ND3 have not been previously reported. The patient is a 32 years-old female with multisystem mitochondrial disease due to variant m.10191T>C in MT-ND3, who has been experiencing episodic, spontaneous or induced abnormal movements since age 23. The abnormal movements started as right hemi-athetosis, bilateral dystonia of the legs, or unilateral dystonia of the right arm and leg. They often progressed to severe ballism, involving the trunk, and limbs. The arms were more dystonic than the legs. In conclusion, complex-I deficiency due to the variant m.10191T>C in MT-ND3 may manifest as multisystem disease including hyperkinesias. Neurologists should be aware of hyperkinesias as a manifestation of complex-I deficiency.


RésuméL'hyperkinésie d'une patiente atteinte d'un déficit en complexe I dû à la variante m.10191T>C du gène MT-ND3 n'a jamais été rapportée auparavant. La patiente est une femme de 32 ans atteinte d'une maladie mitochondriale multisystémique due à la variante m.10191T>C du gène MT-ND3, qui présente des mouvements anormaux épisodiques, spontanés ou provoqués depuis l'âge de 18 ans. mouvements anormaux épisodiques, spontanés ou provoqués depuis l'âge de 23 ans. Les mouvements anormaux ont commencé par une hémiathétose droite, dystonie bilatérale des jambes ou dystonie unilatérale du bras et de la jambe droite. Ils ont souvent évolué vers un ballisme sévère, impliquant le tronc et les membres. le tronc et les membres. Les bras étaient plus dystoniques que les jambes. En conclusion, le déficit en complexe I dû à la variante m.10191T>C du gène MT-ND3 peut se manifester par une maladie multisystémique comprenant des hyperkinésies. Les neurologues doivent être conscients que l'hyperkinésie est une manifestation du déficit en complexe-I. de la déficience en complexe I.


Asunto(s)
Enfermedad de Leigh , Humanos , Femenino , Adulto , Enfermedad de Leigh/complicaciones , Enfermedad de Leigh/diagnóstico , Hipercinesia/etiología , Complejo I de Transporte de Electrón/deficiencia , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/genética , Mutación
6.
J Pharmacol Exp Ther ; 390(2): 250-259, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38866563

RESUMEN

Mutations in the GNAO1 gene, which encodes the abundant brain G-protein Gα o, result in neurologic disorders characterized by developmental delay, epilepsy, and movement abnormalities. There are over 50 mutant alleles associated with GNAO1 disorders; the R209H mutation results in dystonia, choreoathetosis, and developmental delay without seizures. Mice heterozygous for the human mutant allele (Gnao1 +/R209H) exhibit hyperactivity in open field tests but no seizures. We developed self-complementary adeno-associated virus serotype 9 (scAAV9) vectors expressing two splice variants of human GNAO1 Gα o isoforms 1 (GoA, GNAO1.1) and 2 (GoB, GNAO1.2). Bilateral intrastriatal injections of either scAAV9-GNAO1.1 or scAAV9-GNAO1.2 significantly reversed mutation-associated hyperactivity in open field tests. GNAO1 overexpression did not increase seizure susceptibility, a potential side effect of GNAO1 vector treatment. This represents the first report of successful preclinical gene therapy for GNAO1 encephalopathy applied in vivo. Further studies are needed to uncover the molecular mechanism that results in behavior improvements after scAAV9-mediated Gα o expression and to refine the vector design. SIGNIFICANCE STATEMENT: GNAO1 mutations cause a spectrum of developmental, epilepsy, and movement disorders. Here we show that intrastriatal delivery of scAAV9-GNAO1 to express the wild-type Gα o protein reduces the hyperactivity of the Gnao1 +/R209H mouse model, which carries one of the most common movement disorder-associated mutations. This is the first report of a gene therapy for GNAO1 encephalopathy applied in vivo on a patient-allele model.


Asunto(s)
Dependovirus , Subunidades alfa de la Proteína de Unión al GTP Gi-Go , Heterocigoto , Animales , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Ratones , Dependovirus/genética , Humanos , Masculino , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Hipercinesia/genética , Mutación , Terapia Genética/métodos , Ratones Endogámicos C57BL , Locomoción/genética
7.
Mov Disord Clin Pract ; 11(6): 708-715, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38698576

RESUMEN

BACKGROUND: Genetic syndromes of hyperkinetic movement disorders associated with epileptic encephalopathy and intellectual disability are becoming increasingly recognized. Recently, a de novo heterozygous NACC1 (nucleus accumbens-associated 1) missense variant was described in a patient cohort including one patient with a combined mitochondrial oxidative phosphorylation (OXPHOS) deficiency. OBJECTIVES: The objective is to characterize the movement disorder in affected patients with the recurrent c.892C>T NACC1 variant and study the NACC1 protein and mitochondrial function at the cellular level. METHODS: The movement disorder was analyzed on four patients with the NACC1 c.892C>T (p.Arg298Trp) variant. Studies on NACC1 protein and mitochondrial function were performed on patient-derived fibroblasts. RESULTS: All patients had a generalized hyperkinetic movement disorder with chorea and dystonia, which occurred cyclically and during sleep. Complex I was found altered, whereas the other OXPHOS enzymes and the mitochondria network seemed intact in one patient. CONCLUSIONS: The movement disorder is a prominent feature of NACC1-related disease.


Asunto(s)
Hipercinesia , Niño , Femenino , Humanos , Masculino , Hipercinesia/genética , Mitocondrias/genética , Mitocondrias/patología , Mutación Missense , Fosforilación Oxidativa , Proteínas Represoras/genética
9.
Artículo en Inglés | MEDLINE | ID: mdl-38765932

RESUMEN

Background: Subacute Sclerosing Panencephalitis (SSPE) typically presents with periodic myoclonus; however, a spectrum of movement disorders including dystonia, chorea, tremor, and parkinsonism have also been described. This review aims to evaluate the array of movement disorders in SSPE, correlating them with neuroimaging findings, disease stages, and patient outcomes. Methods: A comprehensive review of published case reports and case series was conducted on patients with SSPE exhibiting movement disorders other than periodic myoclonus. PRISMA guidelines were followed, and the protocol was registered with PROSPERO (2023 CRD42023434650). A comprehensive search of multiple databases yielded 37 reports detailing 39 patients. Dyken's criteria were used for SSPE diagnosis, and the International Movement Disorders Society definitions were applied to categorize movement disorders. Results: The majority of patients were male, with an average age of 13.8 years. Approximately, 80% lacked a reliable vaccination history, and 39% had prior measles infections. Dystonia was the most common movement disorder (49%), followed by parkinsonism and choreoathetosis. Rapid disease progression was noted in 64% of cases, with a disease duration of ≤6 months in 72%. Neuroimaging showed T2/FLAIR MR hyperintensities, primarily periventricular, with 26% affecting the basal ganglia/thalamus. Brain biopsies revealed inflammatory and neurodegenerative changes. Over half of the patients (56%) reached an akinetic mute state or died. Conclusion: SSPE is associated with diverse movement disorders, predominantly hyperkinetic. The prevalence of dystonia suggests basal ganglia dysfunction.


Asunto(s)
Trastornos del Movimiento , Panencefalitis Esclerosante Subaguda , Humanos , Corea/fisiopatología , Corea/diagnóstico por imagen , Corea/etiología , Distonía/fisiopatología , Distonía/etiología , Hipercinesia/fisiopatología , Hipercinesia/etiología , Hipocinesia/fisiopatología , Hipocinesia/etiología , Trastornos del Movimiento/fisiopatología , Trastornos del Movimiento/etiología , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/fisiopatología , Panencefalitis Esclerosante Subaguda/fisiopatología , Panencefalitis Esclerosante Subaguda/diagnóstico por imagen , Panencefalitis Esclerosante Subaguda/complicaciones , Informes de Casos como Asunto , Masculino , Femenino , Adolescente
10.
CNS Neurosci Ther ; 30(5): e14739, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38702935

RESUMEN

AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.


Asunto(s)
Antipsicóticos , Aripiprazol , Modelos Animales de Enfermedad , Maleato de Dizocilpina , Hipocampo , Hipercinesia , Esquizofrenia , Animales , Aripiprazol/farmacología , Aripiprazol/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Maleato de Dizocilpina/farmacología , Ratones , Hipercinesia/tratamiento farmacológico , Masculino , Locomoción/efectos de los fármacos , Locomoción/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Ratones Endogámicos C57BL , Animales Recién Nacidos , Neuronas/efectos de los fármacos , Ritmo Teta/efectos de los fármacos , Ritmo Teta/fisiología
11.
Artículo en Inglés | MEDLINE | ID: mdl-38617829

RESUMEN

Background: Spinocerebellar ataxia 21 (SCA21) is a rare neurological disorder caused by heterozygous variants in TMEM240. A growing, yet still limited number of reports suggested that hyperkinetic movements should be considered a defining component of the disease. Case Series: We describe two newly identified families harboring the recurrent pathogenic TMEM240 p.Pro170Leu variant. Both index patients and the mother of the first proband developed movement disorders, manifesting as myoclonic dystonia and action-induced dystonia without co-occurring ataxia in one case, and pancerebellar syndrome complicated by action-induced dystonia in the other. We reviewed the literature on TMEM240 variants linked to hyperkinetic disorders, comparing our cases to described phenotypes. Discussion: Adding to prior preliminary observations, our series highlights the relevance of hyperkinetic movements as clinically meaningful features of SCA21. TMEM240 mutation should be included in the differential diagnosis of myoclonic dystonia and ataxia-dystonia syndromes.


Asunto(s)
Distonía , Trastornos Distónicos , Mioclonía , Degeneraciones Espinocerebelosas , Humanos , Distonía/diagnóstico , Distonía/genética , Mioclonía/diagnóstico , Mioclonía/genética , Hipercinesia , Ataxia , Enfermedades Raras , Síndrome , Proteínas de la Membrana
12.
HGG Adv ; 5(3): 100289, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38571311

RESUMEN

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by pathogenic variants in TCF4, leading to intellectual disability, specific morphological features, and autonomic nervous system dysfunction. Epigenetic dysregulation has been implicated in PTHS, prompting the investigation of a DNA methylation (DNAm) "episignature" specific to PTHS for diagnostic purposes and variant reclassification and functional insights into the molecular pathophysiology of this disorder. A cohort of 67 individuals with genetically confirmed PTHS and three individuals with intellectual disability and a variant of uncertain significance (VUS) in TCF4 were studied. The DNAm episignature was developed with an Infinium Methylation EPIC BeadChip array analysis using peripheral blood cells. Support vector machine (SVM) modeling and clustering methods were employed to generate a DNAm classifier for PTHS. Validation was extended to an additional cohort of 11 individuals with PTHS. The episignature was assessed in relation to other neurodevelopmental disorders and its specificity was examined. A specific DNAm episignature for PTHS was established. The classifier exhibited high sensitivity for TCF4 haploinsufficiency and missense variants in the basic-helix-loop-helix domain. Notably, seven individuals with TCF4 variants exhibited negative episignatures, suggesting complexities related to mosaicism, genetic factors, and environmental influences. The episignature displayed degrees of overlap with other related disorders and biological pathways. This study defines a DNAm episignature for TCF4-related PTHS, enabling improved diagnostic accuracy and VUS reclassification. The finding that some cases scored negatively underscores the potential for multiple or nested episignatures and emphasizes the need for continued investigation to enhance specificity and coverage across PTHS-related variants.


Asunto(s)
Metilación de ADN , Hiperventilación , Discapacidad Intelectual , Factor de Transcripción 4 , Humanos , Factor de Transcripción 4/genética , Hiperventilación/genética , Hiperventilación/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Femenino , Masculino , Niño , Facies , Adolescente , Epigenómica/métodos , Epigénesis Genética , Hipercinesia/genética , Preescolar , Adulto , Adulto Joven
13.
Nervenarzt ; 95(8): 697-703, 2024 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-38630301

RESUMEN

Disorders of the gastrointestinal tract in patients suffering from hypokinetic movement disorders, and in particular Parkinson's disease, have increasingly been the subject of more intensive neuromedical research. So far, few data are available for patients with hyperkinetic movement disorders and ataxias. This review article summarizes the currently available and relevant publications on this topic. The particular focus is on essential tremor, restless legs syndrome, Huntington's disease and the group of hereditary ataxias. Further intensive research will be necessary in the future to collect detailed information also for these disease symptoms about specific disturbance patterns, in order to understand the underlying pathological pathways and to derive specific treatment approaches.


Asunto(s)
Enfermedades Gastrointestinales , Trastornos del Movimiento , Humanos , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/terapia , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/fisiopatología , Trastornos del Movimiento/terapia , Hipercinesia/diagnóstico , Ataxia/diagnóstico , Ataxia/terapia , Ataxia/fisiopatología , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/terapia , Enfermedad de Huntington/fisiopatología , Síndrome de las Piernas Inquietas/diagnóstico , Síndrome de las Piernas Inquietas/terapia , Temblor Esencial/diagnóstico , Temblor Esencial/fisiopatología , Temblor Esencial/terapia
14.
Am J Med Genet A ; 194(9): e63636, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38655717

RESUMEN

Biallelic pathogenic variations in the zinc finger protein 142 (ZNF142) gene are associated with neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM). This disorder is characterized by developmental delay, intellectual disability, speech delay, and movement disorders such as dystonia, tremor, ataxia, and chorea. Here, we report a patient who exhibited common neurological features and rarely reported brain MRI findings. Exome sequencing identified a novel biallelic variant in ZNF142 (c.3528_3529delTG; p.C1176fs*5 (NM_001105537.4)). NEDISHM was first described by Khan et al. (2019) and has been reported in 39 patients to date. Furthermore, upon reviewing our in-house data covering 750 individuals, we identified three different pathogenic ZNF142 variants. It appears that the frequency of ZNF142 alleles is not as low as initially thought, suggesting that this gene should be included in new generation sequencing panels for similar clinical scenarios. Our goal is to compile and expand upon the clinical features observed in NEDISHM, providing novel insights and presenting a new variant to the literature. We also aim to demonstrate that ZNF142 pathogenic variants should be considered in neurodevelopmental diseases.


Asunto(s)
Alelos , Trastornos del Neurodesarrollo , Niño , Humanos , Masculino , Proteínas de Unión al ADN/genética , Secuenciación del Exoma , Predisposición Genética a la Enfermedad , Hipercinesia/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Mutación/genética , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/patología , Fenotipo , Trastornos del Habla/genética , Trastornos del Habla/patología , Factores de Transcripción/genética
15.
Stem Cell Res ; 76: 103371, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452705

RESUMEN

Autosomal dominant neurodevelopmental disorder with or without hyperkinetic movements and seizures (NDHMSD) is a rare neurological disorder characterized by neurodevelopmental disorder and hyperkinetic movement, with or without seizures. Heterozygous mutation in the GRIN1 encoding the subunit 1 of the N-methyl-D-aspartate receptor caused this disorder. We first established an induced pluripotent stem cell (iPSC) line from a male patient with c.389A > G mutation in the GRIN1, via reprogramming with KLF4, SOX2, OCT3/4, and c-MYC. Through identification examination, the iPSCs (GWCMCi006-A) stably expressed pluripotency-associated stem cell markers, maintained a normal karyotype, and showed proliferative potential for three-germ layers differentiation.


Asunto(s)
Células Madre Pluripotentes Inducidas , Humanos , Masculino , Células Madre Pluripotentes Inducidas/metabolismo , Hipercinesia/metabolismo , Factor 4 Similar a Kruppel , Mutación/genética , Diferenciación Celular/genética , Convulsiones , Proteínas del Tejido Nervioso/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo
16.
Neuropediatrics ; 55(4): 217-223, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38442915

RESUMEN

Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which act as intracellular second messengers for signal transduction pathways and modulate various processes in the central nervous system. Recent discoveries that mutations in genes encoding different PDEs, including PDE10A, are responsible for rare forms of chorea in children led to the recognition of an emerging role of PDEs in the field of pediatric movement disorders. A comprehensive literature review of all reported cases of PDE10A mutations in PubMed and Web of Science was performed in English. We included eight studies, describing 31 patients harboring a PDE10A mutation and exhibiting a hyperkinetic movement disorder with onset in infancy or childhood. Mutations in both GAF-A, GAF-B regulatory domains and outside the GAF domains of the PDE10A gene have been reported to cause hyperkinetic movement disorders. In general, patients with homozygous mutations in either GAF-A domain of PDE10A present with a more severe phenotype and at an earlier age but without any extensive abnormalities of the striata compared with patients with dominant variants in GAF-B domain, indicating that dominant and recessive mutations have different pathogenic mechanisms. PDE10A plays a key role in regulating control of striato-cortical movement. Comprehension of the molecular mechanisms within the cAMP and cGMP signaling systems caused by PDE10A mutations may inform novel therapeutic strategies that could alleviate symptoms in young patients affected by these rare movement disorders.


Asunto(s)
Hipercinesia , Mutación , Hidrolasas Diéster Fosfóricas , Humanos , Hidrolasas Diéster Fosfóricas/genética , Hipercinesia/genética , Niño
17.
Neurology ; 102(3): e208079, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38165302

RESUMEN

An 82-year-old man with a history of hypertension and coronary revascularization presented with sudden-onset right hemiparesis and disorientation lasting 5 hours. On admission, he was intubated because of gasping and a Glasgow Coma Scale of 3. Hemorrhagic stroke was suspected, but ruled out by the initial head CT, which revealed old cerebellar lacunae. The following day, the comatose, now unsedated patient exhibited tetraparesis; fixed, nonreactive pupils; and corneal reflex, but no oculocephalic reflex. Rhythmic undulating tongue movements without palatal or limb involvement were first observed (Video 1). EEG revealed no epileptiform activity. Follow-up head CT showed acute ischemic lesions in the thalamocapsular region, midbrain, and pons while angiotomography revealed distal basilar artery occlusion (Figure). Involuntary tongue movements, though rare, have been associated with various conditions such as stroke, trauma, and epilepsy.1,2 These movements may result from disinhibition within the inhibitory reticular formation projecting to hypoglossal neurons, suggesting the pontine reticular formation as a central pacemaker.2.


Asunto(s)
Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular , Anciano de 80 o más Años , Humanos , Masculino , Coma , Hipercinesia , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Lengua
18.
Cuad. psicol. deporte ; 24(1): 80-94, Ene 2, 2024. ilus, tab
Artículo en Inglés | IBECS | ID: ibc-229620

RESUMEN

The aim of thepresent study was to investigate the effectiveness of selected cognitive-motor intervention on the level of physical literacy (PL) and executive functions of Attention-deficit/hyperactivity disorder (ADHD) girls in a one-month follow-up plan. The statistical population included 30 girls with ADHD, all from Yazd (15 participants per group, experimental and control) were selected based on DSM-V criteria. While the control group was not exposed to any treatment andjust continued working as usual, the experimental group participated in 18 sessions (3 sessions a week) of the cognitive-motor program. In order to evaluate PL, the Canadian Assessment of Physical Literacy Second Edition (CAPL-2), and for executive function the Continuous Performance Test (sustained attention) and Computer Mapping of the Tower of London task (motion planning) were used. Data analysis wa also conducted using the mixed varianceanalysis test with repeated measures and an independent T-test at a significance level of p≤.05. According to the results, the experimental group had better performance in PL and executive functions (sustained attention and movement planning) in the posttest and follow-up than the pretest. But, in the control group, no significant difference was observed between the test stages. Moreover, comparing the groups, the experimental group had better performance than the control group in PL, sustained attention, and movement planning. Therefore, cognitive-motor intervention can be used to develop PL and executive functions of ADHD girls.(AU)


El objetivo del estudio fueinvestigar la efectividad de una intervención cognitiva-motora seleccionada en el nivel de la Literacia Física (PL) y funciones ejecutivas de niñas contrastorno por déficit de atención e hiperactividad (TDAH) en un plan de seguimiento de un mes. La población eran niñas con TDAH, de Yazd, 15 participantes por grupo, experimental y control, fueron seleccionadas según los criterios del DSM-V. Mientras que el grupo de control no estuvo expuesto a ningún tratamiento y siguió trabajando como de costumbre, el grupo experimental participó en 18 sesiones del programa cognitivo-motor. (3 sesiones/sem). Para evaluar la PL se utilizó Canadian Assessment of Physical Literacy Second Edition (CAPL-2), y para la función ejecutiva el Continuous Performance Test (atenciónsostenida) y la tarea Computer Mapping of the Tower of London (planificación motora). Un análisis de varianza mixta con medida repetida y una prueba T independiente fue realizada a un nivel de significancia de p≤.05. De acuerdo con los resultados, el grupoexperimental tuvo mejor desempeño en PL y funciones ejecutivas (atención sostenida y planificación motora) en el posprueba y seguimiento que en la prueba previa. Pero, en el grupo de control, no se observó diferencia significativa entre las etapas de laprueba. Al comparar los grupos, se demostró que el grupo experimental tuvo un mejor desempeño que el grupo de control en PL, atención sostenida y planificación motora. Por lo tanto, la intervención cognitivo-motora se puede utilizar para desarrollar la PL y las funciones ejecutivas de las niñas con TDAH.(AU)


O objetivo do presente estudo foi investigar a eficácia da intervenção cognitivo-motora selecionada no nível de Literacia Física (PL) e funções executivas de meninas com transtorno de déficit de atenção/hiperatividade (TDAH) com um plano de acompanhamento de um mês. A população foi composta por 30 meninas meninas com TDAH, todas de Yazd, as quais (15 participantes por grupo, experimental e controlo) foram selecionadas com base nos critérios do DSM-V. Enquanto o grupo controlo não foi exposto a nenhum tratamento e apenas continuou trabalhando normalmente, o grupo experimental participou de 18 sessões do programa cognitivo-motor (3 sessões/semena). Para avaliar a PL, foi utilizado o Canadian Assessment of Physical Literacy Second Edition (CAPL-2), e para a função executiva o Continuous Performance Test (atenção sustentada) e a tarefa de Computer Mapping of the Tower of London (planeamentomotor). A análise dos dados também foi realizada por meio do teste de análise de variância mista com medida repetida e um t test de amsotras independentescom nível designificância p≤.05. De acordo com os resultados, o grupo experimental demonstrou melhor desempenho em PL e funções executivas (atenção sustentada e planeamento motor) no pós-teste do que no pré-teste. Já no grupo controlo não frami observadasdiferenças significativas entre as etapas do teste. A comparação dos grupos evidenciou que o grupoexperimental teve melhor desempenho do que o grupo controlo na alfabetização física, atenção sustentada e planeamento motor. Portanto, a intervenção cognitivo-motora pode ser usada para desenvolver a PL e as funções executivas de meninas com TDAH.(AU)


Asunto(s)
Humanos , Femenino , Niño , Función Ejecutiva , Imagen Corporal/psicología , Motivación , Confianza/psicología , Trastorno por Déficit de Atención con Hiperactividad , Hipercinesia , Psicología , Psicología del Deporte , Medicina Deportiva , Deportes/psicología , Psicología Infantil , Psicología del Desarrollo , Salud Mental
19.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(9. Vyp. 2): 83-86, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-37942977

RESUMEN

Paroxysmal dyskinesia is a clinically and etiologically polymorphic group of diseases, the main clinical manifestation of which is transient attacks of extrapyramidal movements, with different conditions of occurrence. Paroxysmal kinesigenic dyskinesia belongs to the group of primary dyskinesias, which also includes paroxysmal non-kinesigenic dyskinesia and exercise-induced paroxysmal dyskinesia. The most common cause of paroxysmal kinesiogenic dyskinesia is mutations in the PRRT2 gene; in cases of non-kinesiogenic dyskinesia, a mutation in the MR1 gene is detected. The diagnosis of primary dyskinesias causes significant difficulty for clinicians due to the rarity of occurrence, as well as the large spectrum of conditions occurring with paroxysmal motor disorders in childhood. The article describes the clinical observation of 16-year-old twin brothers with transient attacks of dystonic, choreic and ballistic hyperkinesis that suddenly arose during movement. Patients were treated for tics and epilepsy for 12 years. Taking into account the clinical picture - transient attacks of hyperkinesis, their connection with movement, as well as data from video-electroencephalographic monitoring, a diagnosis of paroxysmal kinesiogenic dyskinesia was established, which in a further diagnostic search was confirmed by targeted sequencing of the pathological variant of the PRRT2 gene previously described in patients with kinesiogenic dyskinesia. The administration of carbamazepine, which is the drug of choice in the treatment of this category of patients, has achieved significant control over hyperkinesis in twins. Thus, molecular genetic diagnosis helps confirm the diagnosis of paroxysmal dyskinesias, but careful analysis of the clinical picture, considering the provoking factor, remains the basis of diagnosis.


Asunto(s)
Corea , Discinesias , Masculino , Humanos , Adolescente , Corea/diagnóstico , Corea/tratamiento farmacológico , Corea/genética , Hipercinesia , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Discinesias/diagnóstico , Discinesias/genética
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