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1.
Stem Cell Res ; 76: 103371, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452705

RESUMO

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.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Masculino , Células-Tronco Pluripotentes Induzidas/metabolismo , Hipercinese/metabolismo , Fator 4 Semelhante a Kruppel , Mutação/genética , Diferenciação Celular/genética , Convulsões , Proteínas do Tecido Nervoso/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo
2.
Neurology ; 102(3): e208079, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38165302

RESUMO

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.


Assuntos
Acidente Vascular Cerebral Hemorrágico , Acidente Vascular Cerebral , Idoso de 80 Anos ou mais , Humanos , Masculino , Coma , Hipercinese , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Língua
3.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(9. Vyp. 2): 83-86, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37942977

RESUMO

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.


Assuntos
Coreia , Discinesias , Masculino , Humanos , Adolescente , Coreia/diagnóstico , Coreia/tratamento farmacológico , Coreia/genética , Hipercinese , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Discinesias/diagnóstico , Discinesias/genética
5.
Neurology ; 101(24): 1134-1139, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37857493

RESUMO

We report a case of a 3-year-old boy who presented with abnormal movements that initially occurred only during sleep. Three years later, he went on to develop hyperkinetic movements during the daytime while awake. There was a strong family history of various paroxysmal neurologic disorders. In this report, we discuss the clinical approach, differential diagnosis, investigation, and treatment options for nocturnal hyperkinetic movements and paroxysmal movement disorders.


Assuntos
Discinesias , Transtornos dos Movimentos , Masculino , Humanos , Pré-Escolar , Hipercinese/diagnóstico , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/etiologia , Sono , Raciocínio Clínico
6.
Commun Biol ; 6(1): 985, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752334

RESUMO

Adult male and female schistosomes in copula dwell within human blood vessels and lay eggs that cause the major Neglected Tropical Disease human schistosomiasis. How males and females communicate to each other is poorly understood; however, male-female physical interaction is known to be important. Here, we investigate whether excretory-secretory products (ESPs), released into the external milieu by mature Schistosoma mansoni, might induce responses in the opposite sex. We demonstrate that ESPs adhere to the surface of opposite sex worms inducing the activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways, particularly in the parasite tegument. Furthermore, we show that mature worms stimulated signalling in juvenile worms. Strikingly, we demonstrate that ESPs from the opposite sex promote stem cell proliferation, in an ERK- and p38 MAPK-dependent manner, in the tegument and within the testes of males, and the ovaries and vitellaria of females. Hyperkinesia also occurs following opposite sex ESP exposure. Our findings support the hypothesis that male and female schistosomes may communicate over distance to modulate key processes underlying worm development and disease progression, opening unique avenues for schistosomiasis control.


Assuntos
Hipercinese , Schistosoma mansoni , Adulto , Humanos , Animais , Feminino , Masculino , Transdução de Sinais , Transporte Biológico , MAP Quinases Reguladas por Sinal Extracelular , Proliferação de Células
7.
Soc Neurosci ; 18(6): 331-354, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37580305

RESUMO

Numerous lines of research indicate that our social brain involves a network of cortical and subcortical brain regions that are responsible for sensing and controlling body movements. However, it remains unclear whether movement disorders have a systematic impact on social cognition. To address this question, we conducted a systematic review examining the influence of hyperkinetic movement disorders (including Huntington disease, Tourette syndrome, dystonia, and essential tremor) on social cognition. Following the PRISMA guidelines and registering the protocol in the PROSPERO database (CRD42022327459), we analyzed 50 published studies focusing on theory of mind (ToM), social perception, and empathy. The results from these studies provide evidence of impairments in ToM and social perception in all hyperkinetic movement disorders, particularly during the recognition of negative emotions. Additionally, individuals with Huntington's Disease and Tourette syndrome exhibit empathy disorders. These findings support the functional role of subcortical structures (such as the basal ganglia and cerebellum), which are primarily responsible for movement disorders, in deficits related to social cognition.


Assuntos
Transtornos dos Movimentos , Teoria da Mente , Síndrome de Tourette , Humanos , Cognição Social , Hipercinese , Percepção Social , Cognição , Emoções
9.
Neuropharmacology ; 237: 109630, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37315840

RESUMO

Many patients with Parkinson's disease (PD) experiencing l-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID is unknown. We set out to compare temporal and topographic profiles of abnormal involuntary movements (AIMs) after l-DOPA dose challenges including or not the dopamine agonist ropinirole. Twenty-five patients with PD and a history of dyskinesias were sequentially administered either l-DOPA alone (150% of usual morning dose) or an equipotent combination of l-DOPA and ropinirole in random order. Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS). A sensor-recording smartphone was secured to the patients' abdomen during the test sessions. The two raters' CDRS scores were highly reliable and concordant with models of hyperkinesia presence and severity trained on accelerometer data. The dyskinesia time curves differed between treatments as the l-DOPA-ropinirole combination resulted in lower peak severity but longer duration of the AIMs compared with l-DOPA alone. At the peak of the AIMs curve (60-120 min), l-DOPA induced a significantly higher total hyperkinesia score, whereas in the end phase (240-270 min), both hyperkinesia and dystonia tended to be more severe after the l-DOPA-ropinirole combination (though reaching statistical significance only for the item, arm dystonia). Our results pave the way for the introduction of a combined l-DOPA-ropinirole challenge test in the early clinical evaluation of antidyskinetic treatments. Furthermore, we propose a machine-learning method to predict CDRS hyperkinesia severity using accelerometer data.


Assuntos
Discinesia Induzida por Medicamentos , Distonia , Doença de Parkinson , Humanos , Antiparkinsonianos/efeitos adversos , Agonistas de Dopamina/farmacologia , Discinesia Induzida por Medicamentos/diagnóstico , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/tratamento farmacológico , Hipercinese , Levodopa/efeitos adversos , Oxidopamina , Doença de Parkinson/tratamento farmacológico
10.
J Am Coll Surg ; 237(5): 706-710, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37366537

RESUMO

BACKGROUND: Functional gallbladder disorder is most commonly defined by biliary colic and low ejection fraction (EF) on cholescintigraphy. Biliary hyperkinesia is a controversial type of functional gallbladder disorder, and its definition and the role of cholecystectomy in treating functional gallbladder disorder remains unclear. STUDY DESIGN: We conducted a retrospective review of patients who underwent cholecystokinin-stimulated cholescintigraphy and cholecystectomy at 3 Mayo Clinic sites between 2007 and 2020. Eligible patients were 18 years or older, presented with symptoms of biliary disease, had an EF greater than 50%, underwent cholecystectomy, and had no evidence of acute cholecystitis or cholelithiasis on imaging. We used receiver operating characteristics curve analysis to identify the optimal cutoff value that predicted symptom resolution within 30 days of cholecystectomy. RESULTS: A total of 2,929 cholecystokinin-stimulated cholescintigraphy scans were performed during the study period; the average EF was 67.5% and the median EF was 77%. Analyzing those with EFs greater than or equal to 50% yielded 1,596 patients with 141 (8.8%) going on to have cholecystectomy. No significant differences were found in age, sex, BMI, final pathology between patients with and without pain resolution. Using a cutoff EF of 81% was significantly associated with pain resolution after cholecystectomy (78.2% for EF greater than or equal to 81% vs 60.0% for EF less than 81%, p = 0.03). Chronic cholecystitis was found in 61.7% of the patients on final pathology. CONCLUSIONS: We determined that an EF cutoff of 81% is a reasonable upper limit of normal gallbladder EF. Patients with biliary symptoms and an EF greater than 81% but no evidence of biliary disease on ultrasound or scintigraphy can be classified as having biliary hyperkinesia. Based on our findings, we recommend cholecystectomy for this patient population.


Assuntos
Discinesia Biliar , Doenças da Vesícula Biliar , Humanos , Hipercinese , Colecistectomia/métodos , Doenças da Vesícula Biliar/cirurgia , Colecistocinina , Dor , Estudos Retrospectivos , Discinesia Biliar/diagnóstico por imagem , Discinesia Biliar/cirurgia
12.
Brain Nerve ; 75(5): 542-548, 2023 May.
Artigo em Japonês | MEDLINE | ID: mdl-37194528

RESUMO

Abnormal involuntary movement (AIM) are usually classified into hypokinesia and hyperkinesia group. Hyperkinesia-AIM includes myoclonus, chorea, ballism, dystonia, athetosis, and more. Of these, dystonia, myoclonus, and chorea are frequent movement disorders. From a neurophysiological point of view, the mechanism of motor control by the basal ganglia is thought to consist of three pathways: hyperdirect, direct, and indirect. Hyperkinetic-AIMs are likely caused by the dysfunction of any of these three pathways, leading to malfunction in either presurround inhibition, initiation of motor performance, or postsurround inhibition. These dysfunctions are assumed to stem from regions, such as the cerebral cortex, white matter, basal ganglia, brainstem, and cerebellum. Drug therapies that consider the pathogenesis mechanism are desirable. Here, we presented an overview of treatment methods for hyperkinetic-AIMs.


Assuntos
Coreia , Discinesias , Distonia , Transtornos dos Movimentos , Mioclonia , Humanos , Coreia/terapia , Mioclonia/terapia , Mioclonia/complicações , Distonia/terapia , Distonia/complicações , Hipercinese/complicações
13.
Neurol Sci ; 44(8): 2731-2741, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37043038

RESUMO

BACKGROUND: Several etiologies are responsible for presentation of a twitching tongue in clinical practice. Some of these etiologies cause an isolated hyperkinetic tongue muscle, and some others cause it along with other signs and symptoms. OBJECTIVES: The present paper aims to review the causes, pathology, and presentations reported with twitchy tongue. An anatomical basis of the etiologies responsible for presentation of a twitchy tongue and hyperkinetic movement disorders of this muscle is pursued. METHOD: The reporting of this systematic review was guided by the standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement. All of the research papers conducted with keywords described in the method section between 2000 and 2022 were used, and review articles and articles without any human subject and without any described hyperkinetic movement disorders of the tongue were excluded. RESULTS: All of the etiologies responsible for hyperkinetic movement disorders of tongue were listed in the basis of their anatomical site of effect; cortical region, basal ganglia, cerebellum, brain stem, nucleus and nerve, and neuromuscular junction. One last remained part is the "not classified" section, which contains the etiologies with no particular anatomical origin. CONCLUSION: There are a variety of responsible etiologies for presentation of a twitchy tongue, and in the matter of a complaint of hyperkinetic tongue presentation, physicians should consider anatomical, functional, and psychological etiologies and other signs and symptoms must be participated in the diagnosis process to achieve a proper medical decision.


Assuntos
Hipercinese , Neurologia , Humanos , Gânglios da Base , Tronco Encefálico , Língua
14.
Neurology ; 100(21): e2214-e2223, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37041080

RESUMO

BACKGROUND AND OBJECTIVES: Birk-Landau-Perez syndrome is a genetic disorder caused by biallelic pathogenic variants in SLC30A9 presenting with a complex movement disorder, developmental regression, oculomotor abnormalities, and renal impairment. It has previously been reported in 2 families. We describe the clinical phenotype of 8 further individuals from 4 unrelated families with SLC30A9-related disease. METHOD: Following detailed clinical phenotyping, 1 family underwent research whole-genome sequencing (WGS), 1 research whole-exome sequencing, and 2 diagnostic WGS. Variants of interest were assessed for pathogenicity using in silico prediction tools, homology modeling, and, where relevant, sequencing of complementary DNA (cDNA) for splicing effect. RESULTS: In 2 unrelated families of Pakistani origin (1 consanguineous and 1 not), the same homozygous missense variant in SLC30A9 (c.1253G>T, p.Gly418Val) was identified. Family 1 included 2 affected brothers, and family 2 one affected boy. In family 3, also consanguineous, there were 4 affected siblings homozygous for the variant c.1049delCAG, pAla350del. The fourth family was nonconsanguineous: the 1 affected individual was compound heterozygous for c.1083dup, p.Val362Cysfs*5, and c.1413A>G, p.Ser471=. Despite phenotypic variability between the 4 families, all affected patients manifested with a progressive hyperkinetic movement disorder, associated with oculomotor apraxia and ptosis. None had evidence of severe renal impairment. For the novel missense variant, the conformation of the loop domain and packing of transmembrane helices are likely to be disrupted based on structure modeling. Its presence in 2 unrelated Pakistani families suggests a possible founder variant. For the synonymous variant p.Ser471=, an effect on splicing was confirmed through cDNA analysis. DISCUSSION: Pathogenic variants in SLC30A9 cause a progressive autosomal recessive neurologic syndrome associated with a complex hyperkinetic movement disorder. Our report highlights the expanding disease phenotype, which can present with a wider spectrum of severity than has previously been recognized.


Assuntos
Proteínas de Transporte de Cátions , Hipercinese , Masculino , Humanos , DNA Complementar , Fenótipo , Mutação de Sentido Incorreto/genética , Homozigoto , Linhagem , Fatores de Transcrição , Proteínas de Ciclo Celular
15.
Autism Res ; 16(5): 953-966, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36942618

RESUMO

FOXG1 syndrome is a rare neurodevelopmental disorder associated with severe cognitive dysfunction, autistic behavior, and early-onset hyperkinetic movement disorders. Patients have also been reported to experience sleep disturbances. However, these findings are mainly based on subjective caregivers' reports, and limited by small case numbers. Moreover, no studies using objective evaluation tools, such as actigraphy, have been reported. We analyzed the clinical and sleep manifestations of children with FOXG1 syndrome registered in the FOXG1 Research Foundation Patient Registry database. A total of 258 individuals with FOXG1 syndrome were included in this research. 132 (51.16%) had sleep disturbances. The more impaired of language acquisitions (absence of speech, OR: 3.99, 95%CI = 1.69-9.42, p = 0.002), hyperkinetic movement disorders (OR: 2.64, 95%CI = 1.34-5.20 p = 0.005) and feeding difficulties (OR: 2.81, 95% CI = 1.52-5.19, p = 0.001) were significantly associated with an increase in odds of sleep disturbance after adjusting for age, sex, and antiepileptic drugs. We also performed sleep studies on six individuals with FOXG1 syndrome using The Children's Sleep Habits Questionnaire (CSHQ), the Sleep Disturbance Scale for Children (SDSC), and 7-day data from Actiwatch. The Pittsburgh Sleep Quality Index (PSQI) and 7-day data from Actiwatch were also used to evaluate the sleep condition of their parents. The CSHQ scores revealed bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night-waking, and parasomnia. Sleep-wake transition disorders and disorders of initiating and maintaining sleep were also suggested by the SDSC scores. The children's actigraphy revealed short sleep durations, impaired sleep efficiency, longer wake after sleep onset, and frequent night-waking. All caregivers reported significantly higher PSQI scores, mildly declined sleep efficiency, and shorter total sleep duration. Sleep disturbances, especially in initiating and maintaining sleep, are common in individuals with FOXG1 syndrome and their caregivers. Sleep disorders in patients with FOXG1 syndrome and their caregivers should be investigated.


Assuntos
Transtorno do Espectro Autista , Síndrome de Rett , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Humanos , Criança , Hipercinese , Transtorno do Espectro Autista/complicações , Sono , Síndrome de Rett/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Inquéritos e Questionários , Proteínas do Tecido Nervoso , Fatores de Transcrição Forkhead/genética
16.
Neurol Neurochir Pol ; 57(1): 63-76, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36799521

RESUMO

The aim of this review was to summarise current knowledge regarding hyperkinetic movement disorders related to SARS-CoV-2 infection and vaccination in terms of phenomenology, epidemiology, pathogenesis and treatment. After a thorough review of the PubMed and Google Scholar databases (2020-2022), we identified myoclonus and ataxia sometimes accompanied by opsoclonus (AMS) as the two most frequent COVID-19 sequelae, with chorea, tremor and dystonia being very rare. The pathogenesis seems to be variable, but in the majority of AMS cases it was autoimmunological, with good response and recovery after corticosteroids or intravenous immunoglobulins infusions. Vaccination may be complicated by hyperkinetic movement disorders (e.g. tremor, dystonia), but this is very rare. Patients with Deep Brain Simulation depletion should not be postponed due to lockdowns as this may result in fatal outcomes.


Assuntos
COVID-19 , Distonia , Distúrbios Distônicos , Transtornos dos Movimentos , Humanos , Tremor , Distonia/complicações , Hipercinese/complicações , Hipercinese/terapia , COVID-19/complicações , Controle de Doenças Transmissíveis , SARS-CoV-2 , Distúrbios Distônicos/complicações , Vacinação/efeitos adversos , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/terapia
17.
Eur J Nucl Med Mol Imaging ; 50(7): 1954-1973, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36702928

RESUMO

PURPOSE: To give a comprehensive literature overview of alterations in regional cerebral glucose metabolism, measured using [18F]FDG PET, in conditions associated with hyperkinetic movement disorders and ataxia. In addition, correlations between glucose metabolism and clinical variables as well as the effect of treatment on glucose metabolism are discussed. METHODS: A systematic literature search was performed according to PRISMA guidelines. Studies concerning tremors, tics, dystonia, ataxia, chorea, myoclonus, functional movement disorders, or mixed movement disorders due to autoimmune or metabolic aetiologies were eligible for inclusion. A PubMed search was performed up to November 2021. RESULTS: Of 1240 studies retrieved in the original search, 104 articles were included. Most articles concerned patients with chorea (n = 27), followed by ataxia (n = 25), dystonia (n = 20), tremor (n = 8), metabolic disease (n = 7), myoclonus (n = 6), tics (n = 6), and autoimmune disorders (n = 5). No papers on functional movement disorders were included. Altered glucose metabolism was detected in various brain regions in all movement disorders, with dystonia-related hypermetabolism of the lentiform nuclei and both hyper- and hypometabolism of the cerebellum; pronounced cerebellar hypometabolism in ataxia; and striatal hypometabolism in chorea (dominated by Huntington disease). Correlations between clinical characteristics and glucose metabolism were often described. [18F]FDG PET-showed normalization of metabolic alterations after treatment in tremors, ataxia, and chorea. CONCLUSION: In all conditions with hyperkinetic movement disorders, hypo- or hypermetabolism was found in multiple, partly overlapping brain regions, and clinical characteristics often correlated with glucose metabolism. For some movement disorders, [18F]FDG PET metabolic changes reflected the effect of treatment.


Assuntos
Coreia , Distonia , Transtornos dos Movimentos , Mioclonia , Tiques , Humanos , Fluordesoxiglucose F18 , Coreia/diagnóstico por imagem , Tremor , Hipercinese , Ataxia , Transtornos dos Movimentos/diagnóstico por imagem , Glucose/metabolismo
18.
Artigo em Russo | MEDLINE | ID: mdl-36719128

RESUMO

OBJECTIVE: To study the clinical picture of all patients with GNAO1 encephalopathy detected in the Russian Federation. This publication is a multicenter study combining data from epileptological centers in Moscow, Novosibirsk, St. Petersburg, Nizhny Novgorod, Tyumen. MATERIAL AND METHODS: Nine patients were included, aged 2 to 19 years, with 4 mutations. Male to female sex ratio = 5:4. RESULTS: 8 patients (5 with mutation c.607G>A (p.Gly203Arg), 1 - c.155A>G (Gln52Arg), 1 - c.485G>A (p.Arg162Gln)) had a variant of epileptic encephalopathy, developmental encephalopathy, 1 patient had torsion dystonia without epilepsy (mutation c.713A>G (p.Asp238Gly)). Epileptic seizures in 8 children with epileptic encephalopathy GNAO1 in 100% debuted at 1 month of life, becoming the earliest symptom of the disease. Motor development delayed in 100% of cases. Mental development was not affected only in the case of the dystonic variant. Hyperkinesis (dystonia, choreoathetosis, ballism) followed later, from 2 to 8 months. They were more severe than epilepsy. 4 patients with the c.607G>A (p.Gly203Arg) mutation developed repeated dystonic storms that were resistant to most drugs. CONCLUSION: Epilepsy in GNAO1 is difficult to treat, but temporary or complete remission is possible. Effective drug strategies for the treatment of hyperkinesis have not yet been developed. Expansion of indications for surgical therapy (DBS) of hyperkinesis in this syndrome is desirable.


Assuntos
Encefalopatias , Discinesias , Epilepsia Generalizada , Epilepsia , Criança , Feminino , Humanos , Masculino , Epilepsia/genética , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Hipercinese , Mutação , Convulsões , Pré-Escolar , Adolescente , Adulto Jovem
19.
Neuroimage Clin ; 37: 103302, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36669351

RESUMO

BACKGROUND: Hyperkinetic movement disorders (HMD) manifest as abnormal and uncontrollable movements. Despite reported involvement of several neural circuits, exact connectivity profiles remain elusive. OBJECTIVES: Providing a comprehensive literature review of resting-state brain connectivity alterations using resting-state fMRI (rs-fMRI). We additionally discuss alterations from the perspective of brain networks, as well as correlations between connectivity and clinical measures. METHODS: A systematic review was performed according to PRISMA guidelines and searching PubMed until October 2022. Rs-fMRI studies addressing ataxia, chorea, dystonia, myoclonus, tics, tremor, and functional movement disorders (FMD) were included. The standardized mean difference was used to summarize findings per region in the Automated Anatomical Labeling atlas for each phenotype. Furthermore, the activation likelihood estimation meta-analytic method was used to analyze convergence of significant between-group differences per phenotype. Finally, we conducted hierarchical cluster analysis to provide additional insights into commonalities and differences across HMD phenotypes. RESULTS: Most articles concerned tremor (51), followed by dystonia (46), tics (19), chorea (12), myoclonus (11), FMD (11), and ataxia (8). Altered resting-state connectivity was found in several brain regions: in ataxia mainly cerebellar areas; for chorea, the caudate nucleus; for dystonia, sensorimotor and basal ganglia regions; for myoclonus, the thalamus and cingulate cortex; in tics, the basal ganglia, cerebellum, insula, and frontal cortex; for tremor, the cerebello-thalamo-cortical circuit; finally, in FMD, frontal, parietal, and cerebellar regions. Both decreased and increased connectivity were found for all HMD. Significant spatial convergence was found for dystonia, FMD, myoclonus, and tremor. Correlations between clinical measures and resting-state connectivity were frequently described. CONCLUSION: Key brain regions contributing to functional connectivity changes across HMD often overlap. Possible increases and decreases of functional connections of a specific region emphasize that HMD should be viewed as a network disorder. Despite the complex interplay of physiological and methodological factors, this review serves to gain insight in brain connectivity profiles across HMD phenotypes.


Assuntos
Coreia , Distonia , Distúrbios Distônicos , Mioclonia , Tiques , Humanos , Tremor , Imageamento por Ressonância Magnética , Hipercinese/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Ataxia , Vias Neurais
20.
J Neurochem ; 164(2): 121-142, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36184945

RESUMO

Parkinson's disease (PD) is a heterogeneous multi-systemic disorder unique to humans characterized by motor and non-motor symptoms. Preclinical experimental models of PD present limitations and inconsistent neurochemical, histological, and behavioral readouts. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD is the most common in vivo screening platform for novel drug therapies; nonetheless, behavioral endpoints yielded amongst laboratories are often discordant and inconclusive. In this study, we characterized neurochemically, histologically, and behaviorally three different MPTP mouse models of PD to identify translational traits reminiscent of PD symptomatology. MPTP was intraperitoneally (i.p.) administered in three different regimens: (i) acute-four injections of 20 mg/kg of MPTP every 2 h; (ii) sub-acute-one daily injection of 30 mg/kg of MPTP for 5 consecutive days; and (iii) chronic-one daily injection of 4 mg/kg of MPTP for 28 consecutive days. A series of behavioral tests were conducted to assess motor and non-motor behavioral changes including anxiety, endurance, gait, motor deficits, cognitive impairment, circadian rhythm and food consumption. Impairments in balance and gait were confirmed in the chronic and acute models, respectively, with the latter showing significant correlation with lesion size. The sub-acute model, by contrast, presented with generalized hyperactivity. Both, motor and non-motor changes were identified in the acute and sub-acute regime where habituation to a novel environment was significantly reduced. Moreover, we report increased water and food intake across all three models. Overall, the acute model displayed the most severe lesion size, while across the three models striatal dopamine content (DA) did not correlate with the behavioral performance. The present study demonstrates that detection of behavioral changes following MPTP exposure is challenging and does not correlate with the dopaminergic lesion extent.


Assuntos
Doença de Parkinson , Camundongos , Animais , Humanos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Dopamina , Modelos Animais de Doenças , Hipercinese , Camundongos Endogâmicos C57BL
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