RESUMO
OBJECTIVE: Schizencephaly is a rare congenital malformation that causes motor impairment. To determine the treatment strategy, each domain of the motor functions should be appropriately evaluated. We correlated a color map of diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) with the hand function test (HFT) to identify the type of hand function that each test (DTI and TMS) reflects. Further, we attempted to demonstrate the motor neuron organization in schizencephaly. METHOD: This retrospective study was conducted on 12 patients with schizencephaly. TMS was conducted in the first dorsal interosseous (FDI), biceps (BB), and deltoid muscles of the upper extremity, and contralateral MEP (cMEP) and ipsilateral MEP (iMEP) were recorded. The HFT included the grip strength, box and block (B&B), and 9-hole peg test. The schizencephalic cleft was confirmed using magnetic resonance imaging, and the corticospinal tract (CST) was identified using the color map of DTI. The symmetry indices for the peduncle and CST at pons level were calculated as the ratios of the cross-sectional area of the less-affected side and that of the more-affected side. RESULT: In the more-affected hemisphere TMS, no iMEP was obtained. In the less-affected hemisphere TMS, the iMEP response was detected in 9 patients and cMEP in all patients, which was similar to the pattern observed in unilateral lesion. Paretic hand grip strength was strongly correlated with the presence of iMEP (p = 0.044). The symmetry index of the color map of DTI was significantly correlated with the B&B (p = 0.008, R 2 = 0.416), whereas the symmetry index of the peduncle was not correlated with all HFTs. CONCLUSION: In patients with schizencephaly, the iMEP response rate is correlated with the hand function related to strength, while the symmetricity of the CST by the color map of DTI is correlated with the hand function associated with dexterity. Additionally, we suggest the possible motor organization pattern of schizencephaly following interhemispheric competition.
Assuntos
Pedúnculo Cerebral/patologia , Mãos/fisiopatologia , Córtex Motor/patologia , Ponte/patologia , Transtornos Psicomotores/patologia , Tratos Piramidais/patologia , Esquizencefalia/patologia , Adolescente , Adulto , Mapeamento Encefálico , Pedúnculo Cerebral/diagnóstico por imagem , Pedúnculo Cerebral/fisiopatologia , Criança , Pré-Escolar , Imagem de Tensor de Difusão/métodos , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/fisiopatologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiopatologia , Ponte/diagnóstico por imagem , Ponte/fisiopatologia , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/fisiopatologia , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/fisiopatologia , Estudos Retrospectivos , Esquizencefalia/diagnóstico por imagem , Esquizencefalia/fisiopatologia , Estimulação Magnética Transcraniana/métodosRESUMO
BACKGROUND: Cervical dystonia (CD) is the most common form of focal dystonia with involuntary movements and postures of the head. The pathogenesis and neural mechanisms underlying CD have not been fully elucidated. METHODS: Twenty-seven newly drug-naïve patients with CD and 21 healthy controls (HCs) were recruited with clinical assessment and resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Severity of CD was measured by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui scores. Whole-brain voxel-wise intrinsic connectivity (IC) and seed-based functional connectivity (FC) analyses were performed for detection of changes in the CD group relative to HCs, controlling for age, gender, and global time series correlation, followed by correlation analyses of IC, seed-based FC and clinically relevant features, respectively. RESULTS: In comparison with HCs, CD patients showed significantly increased IC measurement in the anterior part of the left supramarginal gyrus and extended to the inferior left postcentral gyrus (AL-SMG/IL-PCG). With this cluster as a seed, decreased FC was found in the right precentral and postcentral gyrus. Moreover, the regional IC value in the AL-SMG/IL-PCG was significantly positively correlated with TWSTRS-1 (severity) score, and significantly negatively correlated with the associated seed-based FC strength. CONCLUSIONS: Our results showed signs of both hyper- and hypo-connectivity in bilateral regions of the sensorimotor network related to CD. The imbalance of functional connectivity (both hyper- and hypo-) may hint both overloading and disrupted somatosensory or sensorimotor integration dysfunction within the sensorimotor network underlying the pathophysiology of CD, thus providing a network target for future therapies.
Assuntos
Imageamento por Ressonância Magnética , Rede Nervosa/fisiopatologia , Transtornos Psicomotores/fisiopatologia , Torcicolo/fisiopatologia , Adulto , Estudos de Casos e Controles , Correlação de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/etiologia , Córtex Sensório-Motor/diagnóstico por imagem , Córtex Sensório-Motor/fisiopatologia , Índice de Gravidade de Doença , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiopatologia , Torcicolo/complicações , Torcicolo/diagnóstico por imagemRESUMO
Fumarase deficiency (FD) is a rare and severe autosomal disorder, caused by inactivity of the enzyme fumarase, due to biallelic mutations of the fumarase hydratase (FH) gene. Several pathogenic mutations have been published. The article describes an infant with failure to thrive, microcephaly, axial hypotonia, and developmental retardation with increased excretion of fumarate, no activity of fumarase and a homozygous mutation of the FH gene, which was until recently only known as a variant of unknown significance. Carriers of pathogenic mutations in the FH gene are at risk for developing renal cell carcinoma and should therefore be screened. Both parents were healthy carriers of the mutation and had decreased levels of enzyme activity. In addition, the article presents an overview and analysis of all cases of FD reported thus far in the literature.
Assuntos
Fumarato Hidratase/deficiência , Fumarato Hidratase/genética , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/patologia , Hipotonia Muscular/genética , Hipotonia Muscular/patologia , Transtornos Psicomotores/genética , Transtornos Psicomotores/patologia , Humanos , Lactente , Masculino , Erros Inatos do Metabolismo/diagnóstico por imagem , Hipotonia Muscular/diagnóstico por imagem , Transtornos Psicomotores/diagnóstico por imagemAssuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Epilepsia/genética , Predisposição Genética para Doença , Megalencefalia/genética , Poli-Hidrâmnios/genética , Transtornos Psicomotores/genética , Criança , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/diagnóstico por imagem , Epilepsia/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Megalencefalia/diagnóstico , Megalencefalia/diagnóstico por imagem , Megalencefalia/patologia , Linhagem , Poli-Hidrâmnios/diagnóstico , Poli-Hidrâmnios/diagnóstico por imagem , Poli-Hidrâmnios/patologia , Gravidez , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/patologiaRESUMO
Mutations in the ANO3 gene have been associated with autosomal dominant craniocervical dystonia. However, little else is known about the genotype-phenotype characteristics of this disorder. Here we describe a 3 years-old girl with distal myoclonic dystonia. Whole exome sequencing in trio revealed a de novo missense ANO3 variant not previously described in international databases. A global psychomotor regression was observed once dystonia was present. Brain MRI changes paralleled these findings: whereas MRI at the age of 18 months was normal, mild brain and cerebellar atrophy was observed 18 months later. These results suggest that missense mutations in ANO3 may underlie complex disorders particularly characterized by early psychomotor regression and dystonia.
Assuntos
Anoctaminas/genética , Encefalopatias/genética , Distúrbios Distônicos/genética , Transtornos Psicomotores/genética , Idade de Início , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Cerebelo/diagnóstico por imagem , Pré-Escolar , Distúrbios Distônicos/diagnóstico por imagem , Distúrbios Distônicos/patologia , Feminino , Humanos , Mutação de Sentido Incorreto , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/patologiaRESUMO
In 1874, Karl Kahlbaum described catatonia as an independent syndrome characterized by motor, affective, and behavioral anomalies. In the following years, various catatonia concepts were established with all sharing the prime focus on motor and behavioral symptoms while largely neglecting affective changes. In 21st century, catatonia is a well-characterized clinical syndrome. Yet, its neurobiological origin is still not clear because methodological shortcomings of hitherto studies had hampered this challenging effort. To fully capture the clinical picture of catatonia as emphasized by Karl Kahlbaum, 2 decades ago a new catatonia scale was developed (Northoff Catatonia Rating Scale [NCRS]). Since then, studies have used NCRS to allow for a more mechanistic insight of catatonia. Here, we undertook a systematic review searching for neuroimaging studies using motor/behavioral catatonia rating scales/criteria and NCRS published up to March 31, 2019. We included 19 neuroimaging studies. Studies using motor/behavioral catatonia rating scales/criteria depict cortical and subcortical motor regions mediated by dopamine as neuronal and biochemical substrates of catatonia. In contrast, studies relying on NCRS found rather aberrant higher-order frontoparietal networks which, biochemically, are insufficiently modulated by gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission. This is further supported by the high therapeutic efficacy of GABAergic agents in acute catatonia. In sum, this systematic review points out the difference between motor/behavioral and NCRS-based classification of catatonia on both neuronal and biochemical grounds. That highlights the importance of Kahlbaum's original truly psychomotor concept of catatonia for guiding both research and clinical diagnosis and therapy.
Assuntos
Encéfalo , Catatonia , Transtornos Psicomotores , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Catatonia/classificação , Catatonia/diagnóstico por imagem , Catatonia/metabolismo , Catatonia/fisiopatologia , Humanos , Transtornos Psicomotores/classificação , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/metabolismo , Transtornos Psicomotores/fisiopatologiaRESUMO
Serine deficiency disorders can result from deficiency in one of three enzymes. Deficiency of the second enzyme, 3-phosphoserine aminotransferase (PSAT), has been reported in two siblings; the eldest investigated for acquired microcephaly, spasticity and epilepsy. Our patient had neurological symptoms at birth. Fetal magnetic resonance imaging (MRI) at 35-week gestation demonstrated microencephaly and gyral simplification (anterior > posterior) which was confirmed upon postnatal MRI. Congenital microcephaly was apparent at birth. PSAT deficiency was confirmed when exome sequencing identified biallelic mutations in PSAT1 and biochemical testing noted low plasma serine and cerebral spinal fluid serine. Despite oral serine and glycine supplementation at 4 months old, the patient showed little neurodevelopmental progress and developed epileptic spasms at 10 months old. PSAT deficiency should be considered for patients with congenital microcephaly. Although further characterization of MRI findings in other patients is required, microencephaly with simplified gyral pattern could provide imaging clues for this rare metabolic disorder.
Assuntos
Imageamento por Ressonância Magnética , Microcefalia/etiologia , Diagnóstico Pré-Natal/métodos , Transtornos Psicomotores/diagnóstico por imagem , Convulsões/diagnóstico por imagem , Transaminases/deficiência , Feminino , Humanos , Lactente , Recém-Nascido , Microcefalia/complicações , Microcefalia/diagnóstico por imagem , Gravidez , Transtornos Psicomotores/complicações , Convulsões/complicaçõesRESUMO
Hypoxia exposure during high-altitude expedition cause psychomotor impairment. Neuroimaging studies indicated that the impairment may be significantly associated with neuron loss and decreased regional homogeneity (ReHo) in several brain regions, suggesting the neural functionality in these regions may be utilized to predict psychomotor impairment under exposure. In this study, 69 subjects come from Shaanxi-Tibet immigrant cohort. Reaction time (RT) tasks were performed to measure the subject's psychomotor function before and after 2-year high-altitude exposure. For each individual, the RT differences between pre-exposure and post-exposure were calculated, which were referred to as "targets" in model establishment. Rs-fMRI data were acquired at the same time with RT tasks. For each individual, the map of ReHo alteration was generated, from which the patterns would be recognized. A pattern recognition procedure was utilized to train and test the predictive models. Two different cross-validation strategies were utilized to evaluate the model performance: leave-one-out cross-validation and four-fold cross-validation. For the models displaying significant R2 and MSE, weight maps were built. As a result, the predictive models were able to decode the changes of simple and recognition reaction time from the alterations of brain activation under the exposure. The regions with highest contributions to the predictions were bilateral putamen and bilateral pallidum, suggesting that predictions were mainly based on the patterns concentrated in these regions. This study was a proof of concept study designed to examine whether individual-level psychomotor impairment under high-altitude exposure could be predicted by a combination of pattern recognition approach and neuroimaging data.
Assuntos
Doença da Altitude/fisiopatologia , Globo Pálido/fisiopatologia , Transtornos Psicomotores/fisiopatologia , Putamen/fisiopatologia , Adolescente , Doença da Altitude/diagnóstico por imagem , Feminino , Globo Pálido/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Masculino , Reconhecimento Automatizado de Padrão , Transtornos Psicomotores/diagnóstico por imagem , Putamen/diagnóstico por imagem , Adulto JovemAssuntos
Códon sem Sentido , Anormalidades Craniofaciais , Heterozigoto , Histona Acetiltransferases/genética , Deficiência Intelectual , Rim/anormalidades , Patela/anormalidades , Transtornos Psicomotores , Escroto/anormalidades , Tomografia Computadorizada por Raios X , Anormalidades Urogenitais , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Anormalidades Craniofaciais/cirurgia , Humanos , Lactente , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Deficiência Intelectual/cirurgia , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Masculino , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/genética , Neuroblastoma/patologia , Neuroblastoma/cirurgia , Patela/diagnóstico por imagem , Patela/patologia , Patela/cirurgia , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/genética , Transtornos Psicomotores/patologia , Transtornos Psicomotores/cirurgia , Escroto/diagnóstico por imagem , Escroto/patologia , Escroto/cirurgia , Anormalidades Urogenitais/diagnóstico por imagem , Anormalidades Urogenitais/genética , Anormalidades Urogenitais/patologia , Anormalidades Urogenitais/cirurgiaRESUMO
Early-onset epileptic encephalopathies (EOEEs) are a genetically heterogeneous collection of severe epilepsies often associated with psychomotor regression. Mutations in SZT2, a known seizure threshold regulator gene, are a newly identified cause of EOEE. We present an individual with EOEE, macrocephaly, and developmental regression with compound heterozygous mutations in SZT2 as identified by whole exome sequencing. Serial imaging characterized the novel finding of progressive loss of central myelination. This case expands our clinical understanding of the SZT2-phenotype and emphasizes the role of this gene in the diagnostic investigation for EOEE and leukoencephalopathies.
Assuntos
Leucoencefalopatias/genética , Mutação , Proteínas do Tecido Nervoso/genética , Espasmos Infantis/genética , Sistemas de Transporte de Aminoácidos Acídicos/deficiência , Sistemas de Transporte de Aminoácidos Acídicos/genética , Antiporters/deficiência , Antiporters/genética , Pré-Escolar , Deficiências do Desenvolvimento/genética , Feminino , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico por imagem , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/etiologia , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Heterozigoto , Humanos , Lactente , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/etiologia , Imageamento por Ressonância Magnética , Megalencefalia/diagnóstico por imagem , Megalencefalia/genética , Doenças Mitocondriais/diagnóstico por imagem , Doenças Mitocondriais/etiologia , Doenças Mitocondriais/genética , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/etiologia , Transtornos Psicomotores/genética , Espasmos Infantis/diagnóstico por imagem , Espasmos Infantis/etiologiaRESUMO
Emerging evidence suggests that structural brain abnormalities may play a role in the pathophysiology of melancholic depression. We set out to test whether diffusion-derived estimates of white matter structure were disrupted in melancholia in regions underpinning psychomotor function. We hypothesized that those with melancholia (and evidencing impaired psychomotor function) would show disrupted white matter organization in internal capsule subdivisions. Diffusion magnetic resonance imaging (dMRI) data were acquired from 22 melancholic depressed, 23 non-melancholic depressed, and 29 healthy control participants. Voxel-wise fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) values were derived for anterior, posterior, and retrolenticular limbs of the internal capsule and compared between groups. Neuropsychological (reaction time) and psychomotor functioning were assessed and correlated against FA. Fractional anisotropy was distinctly increased, whilst RD was decreased, in the right anterior internal capsule in those with melancholia, compared to controls. The right anterior limb of the internal capsule correlated with clinical ratings of psychomotor disturbance, and reduced psychomotor speed was associated with increased FA values in the right retrolenticular limb in those with melancholia. Our findings highlight a distinct disturbance in the local white matter arrangement in specific regions of the internal capsule in melancholia, which in turn is associated with psychomotor dysfunction. This study clarifies the contribution of structural brain integrity to the phenomenology of melancholia, and may assist future efforts seeking to integrate neurobiological markers into depression subtyping.
Assuntos
Transtorno Depressivo/diagnóstico por imagem , Cápsula Interna/diagnóstico por imagem , Transtornos Psicomotores/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Idoso , Transtorno Depressivo/patologia , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Humanos , Cápsula Interna/patologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Transtornos Psicomotores/patologia , Índice de Gravidade de Doença , Substância Branca/patologia , Adulto JovemRESUMO
OBJECTIVE: Infants ≤28 GA are at particular risk of psychomotor and neurological developmental disorder. They also remain at a higher risk of developing autism spectrum disorder (ASD), characterized by persistent deficits in communication/social interactions and restricted, repetitive behaviors, activities and interests. Monitoring their development by a team of specialists (a neurologist, psychologist, psychiatrist) allows us to make an early diagnosis and to implement appropriate therapy. Neuroimaging studies during the neonatal period may be helpful in clarifying diagnosis and prognosis. Objective: The aim of the study was to search for the interrelation between the results of neuroimaging and the neurological, psychological and psychiatric evaluation at the age of 2. PATIENTS AND METHODS: Material and methods: Neonates born at ≤28 weeks between 01.06.2013 and 31.12.2015 and hospitalized at NICU were enrolled. We present the results of the first 12 children who have attained 2 years of corrected age and have undergone both neuroimaging, and neurological, psychological and psychiatric assessments. Transfontanel ultrasound was performed according to general standards, MRI between 38 and 42 weeks of corrected age. Neurological examination based on the Denver scale, ASD screening with use of the STAT test and psychological DSR assessment were performed at 2 years of corrected age. RESULTS: Results: Median GA was 26 weeks and median weight 795 g. The ultrasound examination was normal in 9 cases (75%) and MRI in 4 (33%). Abnormalities in the cerebellum were the main additional information found in MRI as compared to US. Neurological examination was normal in 8 infants (67#37;), in 4 of whom neuroimaging was normal. In 4 (33%) infants the neurological examination was abnormal. Psychomotor development at an average level or above was found in seven (58#37;) children. In 4 of them neuroimaging was normal, whereas 3 had ventricular dilatation and haemorrhagic infarct. There were no abnormalities within the cerebellum in this group. In the remaining 5 children (42#37;) psychomotor development was rated as delayed. All of them had cerebellar haemorrhage. An increased risk of ASD was observed in 4 children who developed cerebellar hemorrhage. CONCLUSION: Conclusions: 1. The use of MRI at a term-equivalent age may contribute to the prognosis of neurodevelopmental outcomes in extremely premature infants, allowing risk stratification and thus enhancing early monitoring of a child's development and functional status 2. There is a clear tendency towards abnormal psychomotor development and positive screening for ASD to co-occur with abnormal MRI findings in the cerebellum.
Assuntos
Transtorno do Espectro Autista/fisiopatologia , Encéfalo/crescimento & desenvolvimento , Neuroimagem , Transtornos Psicomotores/fisiopatologia , Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Pré-Escolar , Feminino , Humanos , Lactente Extremamente Prematuro , Imageamento por Ressonância Magnética , Masculino , Dados Preliminares , Estudos Prospectivos , Transtornos Psicomotores/diagnóstico por imagem , UltrassonografiaAssuntos
Sistemas de Transporte de Aminoácidos Acídicos/deficiência , Antiporters/deficiência , Distonia/etiologia , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/fisiopatologia , Doenças Mitocondriais/fisiopatologia , Transtornos Psicomotores/fisiopatologia , Síndrome de Sturge-Weber/complicações , Criança , Distonia/diagnóstico por imagem , Distonia/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Doenças Mitocondriais/diagnóstico por imagem , Transtornos Psicomotores/diagnóstico por imagem , Síndrome de Sturge-Weber/diagnóstico por imagem , Síndrome de Sturge-Weber/genética , Tomografia Computadorizada por Raios X , Tubulina (Proteína)/genéticaRESUMO
We aimed to assess the brain signature of cognitive and behavioral impairment in C9orf72-negative non-demented ALS patients. The study included 50 amyotrophic lateral sclerosis (ALS) patients (out of 75 initially recruited) and 38 healthy controls. High-resolution T1-weighted and spin-echo diffusion tensor images were acquired in a 3T MRI scanner. The multi atlas-based analysis protocol and the FreeSurfer tool were employed for gray matter assessment, and fiber tractography for white matter evaluation. Cognitively impaired ALS patients (n = 12) had bilateral amygdalae and left thalamic volumetric reduction compared to non-impaired ALS patients. Behaviorally impaired ALS patients (n = 14) had lower fractional anisotropy (FA) at the fornix in comparison with healthy subjects. These parameters did correlate with cognitive/behavioral scores, but not with motor-functional parameters in the ALS cohort. We believe that basal ganglia and fornix damage might be related to cognitive and behavioral impairment across ALS-frontotemporal dementia continuum. Also, distinct anatomical areas seem to influence the behavioral and cognitive status of these individuals.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Transtornos Psicomotores/diagnóstico por imagem , Idoso , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/fisiopatologia , Anisotropia , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Proteína C9orf72 , Estudos de Casos e Controles , Cognição , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Estudos de Coortes , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicomotores/etiologia , Transtornos Psicomotores/fisiopatologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologiaAssuntos
Deficiências do Desenvolvimento , Oligossacarídeos/urina , Transtornos Psicomotores , Pré-Escolar , Consanguinidade , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/urina , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/etiologia , Transtornos Psicomotores/urinaRESUMO
OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations. METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression. RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy. The majority of patients had a known Roma ethnic background. Single nucleotide polymorphism array analysis in 5 patients identified one large overlapping homozygous region on chromosome 13. WES in 2 patients revealed a homozygous deletion in the promoter region of UFM1. Sanger sequencing confirmed homozygosity for this variant in all 16 patients. All patients shared a common haplotype, indicative of a founder effect. Screening of 1,000 controls from different European Roma panels demonstrated an overall carrier rate of the mutation of 3%-25%. Transfection assays showed that the deletion significantly reduced expression in specific CNS cell lines. CONCLUSIONS: UFM1 encodes ubiquitin-fold modifier 1 (UFM1), a member of the ubiquitin-like family involved in posttranslational modification of proteins. Its exact biological role is unclear. This study associates a UFM1 gene defect with a disease and sheds new light on possible UFM1 functional networks.
Assuntos
Sistemas de Transporte de Aminoácidos Acídicos/deficiência , Antiporters/deficiência , Gânglios da Base/patologia , Cerebelo/patologia , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Doenças Mitocondriais/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Transtornos Psicomotores/genética , Adolescente , Adulto , Sistemas de Transporte de Aminoácidos Acídicos/genética , Antiporters/genética , Atrofia/etiologia , Gânglios da Base/diagnóstico por imagem , Linhagem Celular Tumoral/patologia , Cerebelo/diagnóstico por imagem , Criança , Pré-Escolar , Análise Mutacional de DNA , Saúde da Família , Feminino , Células HeLa , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/complicações , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Itália , Imageamento por Ressonância Magnética , Masculino , Doenças Mitocondriais/complicações , Doenças Mitocondriais/diagnóstico por imagem , Transtornos Psicomotores/complicações , Transtornos Psicomotores/diagnóstico por imagem , Transfecção , Tubulina (Proteína)/genética , Adulto JovemRESUMO
Serine biosynthesis defects can present in a broad phenotypic spectrum ranging from Neu-Laxova syndrome, a lethal disease with multiple congenital anomalies at the severe end, to an infantile disease with severe psychomotor retardation and seizures as an intermediate phenotype, to a childhood disease with intellectual disability at the mild end. In this report we present 6 individuals from 3 families with infantile phosphoglycerate dehydrogenase (PGDH) deficiency who presented with psychomotor delay, growth failure, microcephaly, and spasticity. The phenotype was variable with absence of seizures in 2 sisters in family 1 and 1 infant in family 2 and seizures with pronounced happy affect in 3 sisters in family 3. The initiation of serine treatment had pronounced effect on seizures and spasticity in the sisters in family 3, but minimal developmental effects on the children in families 1 and 2. With such phenotypic variability, the diagnosis of PGDH deficiency can be challenging.
Assuntos
Anormalidades Múltiplas , Encefalopatias , Erros Inatos do Metabolismo dos Carboidratos/complicações , Retardo do Crescimento Fetal , Ictiose , Deformidades Congênitas dos Membros , Microcefalia/complicações , Mutação/genética , Fosfoglicerato Desidrogenase/deficiência , Fosfoglicerato Desidrogenase/genética , Transtornos Psicomotores/complicações , Convulsões/complicações , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/etiologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/terapia , Adolescente , Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Encefalopatias/genética , Encefalopatias/terapia , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico por imagem , Erros Inatos do Metabolismo dos Carboidratos/genética , Pré-Escolar , Saúde da Família , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/etiologia , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/terapia , Humanos , Ictiose/diagnóstico por imagem , Ictiose/etiologia , Ictiose/genética , Ictiose/terapia , Lactente , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/etiologia , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/terapia , Masculino , Microcefalia/diagnóstico por imagem , Microcefalia/etiologia , Microcefalia/genética , Microcefalia/terapia , Fenótipo , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/genética , Convulsões/diagnóstico por imagem , Convulsões/genética , Serina/biossíntese , Adulto JovemRESUMO
Huntington's disease (HD) is a genetically-determined neurodegenerative disease. Characterising neuropathology in mouse models of HD is commonly restricted to cross-sectional ex vivo analyses, beset by tissue fixation issues. In vivo longitudinal magnetic resonance imaging (MRI) allows for disease progression to be probed non-invasively. In the HdhQ150 mouse model of HD, in vivo MRI was employed at two time points, before and after the onset of motor signs, to assess brain macrostructure and white matter microstructure. Ex vivo MRI, immunohistochemistry, transmission electron microscopy and behavioural testing were also conducted. Global brain atrophy was found in HdhQ150 mice at both time points, with no neuropathological progression across time and a selective sparing of the cerebellum. In contrast, no white matter abnormalities were detected from the MRI images or electron microscopy images alike. The relationship between motor function and MR-based structural measurements was different for the HdhQ150 and wild-type mice, although there was no relationship between motor deficits and histopathology. Widespread neuropathology prior to symptom onset is consistent with patient studies, whereas the absence of white matter abnormalities conflicts with patient data. The myriad reasons for this inconsistency require further attention to improve the translatability from mouse models of disease.
Assuntos
Encéfalo/diagnóstico por imagem , Doença de Huntington/diagnóstico por imagem , Transtornos Psicomotores/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Animais , Atrofia , Peso Corporal , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Mapeamento Encefálico , Modelos Animais de Doenças , Progressão da Doença , Expressão Gênica , Humanos , Proteína Huntingtina , Doença de Huntington/genética , Doença de Huntington/patologia , Doença de Huntington/fisiopatologia , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Transtornos Psicomotores/genética , Transtornos Psicomotores/patologia , Transtornos Psicomotores/fisiopatologia , Desempenho Psicomotor , Especificidade da Espécie , Substância Branca/metabolismoAssuntos
Homozigoto , Proteínas Mitocondriais/genética , Mutação , Fenótipo , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genética , Pré-Escolar , Efeito Fundador , Transtornos do Crescimento/diagnóstico por imagem , Transtornos do Crescimento/genética , Hérnia/diagnóstico por imagem , Hérnia/genética , Humanos , Lactente , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/genética , Masculino , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Transtornos Psicomotores/diagnóstico por imagem , Transtornos Psicomotores/genética , Análise de SobrevidaRESUMO
OBJECTIVES: Cognitive impairment is common in Parkinson's disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. METHODS: We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. RESULTS: PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson's disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. CONCLUSIONS: Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson's disease.