RESUMO
OBJECTIVE: To carry out clinical and genetic analysis for a child featuring Brain-Lung-Thyroid syndrome (BLTS). METHODS: A child who had presented at the Children's Hospital Affiliated to Shandong University on May 27, 2022 was selected as the study subject. Clinical data was collected. Trio-whole exome sequencing (Trio-WES) was carried out for the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The child was given individualized treatment following the diagnosis. RESULTS: The child, a two-year-and-seven-month-old boy, had presented with global developmental delay, ataxia and hypothyroidism. WES revealed that he has harbored a heterozygous c.674C>T variant of the NKX2-1 gene, based on which he was diagnosed with BLTS. CT scan revealed interstitial and parenchymal inflammation in his lungs, which was reduced by budesonide aerosol inhalation. CONCLUSION: Discovery of the novel c.674C>T variant has enriched the mutational spectrum of the NKX2-1 gene. Budesonide aerosol may be used to treat lung inflammation associated with BLTS.
Assuntos
Fator Nuclear 1 de Tireoide , Humanos , Masculino , Fator Nuclear 1 de Tireoide/genética , Pré-Escolar , Atetose/genética , Mutação , Sequenciamento do Exoma , Coreia/genética , Povo Asiático/genética , População do Leste Asiático , Hipotireoidismo Congênito , Síndrome do Desconforto Respiratório do Recém-NascidoRESUMO
OBJECTIVE: We aimed to characterize the phenotypic spectrum and functional consequences associated with variants in the gene GABRB2, coding for the γ-aminobutyric acid type A (GABAA ) receptor subunit ß2. METHODS: We recruited and systematically evaluated 25 individuals with variants in GABRB2, 17 of whom are newly described and 8 previously reported with additional clinical data. Functional analysis was performed using a Xenopus laevis oocyte model system. RESULTS: Our cohort of 25 individuals from 22 families with variants in GABRB2 demonstrated a range of epilepsy phenotypes from genetic generalized epilepsy to developmental and epileptic encephalopathy. Fifty-eight percent of individuals had pharmacoresistant epilepsy; response to medications targeting the GABAergic pathway was inconsistent. Developmental disability (present in 84%) ranged from mild intellectual disability to severe global disability; movement disorders (present in 44%) included choreoathetosis, dystonia, and ataxia. Disease-associated variants cluster in the extracellular N-terminus and transmembrane domains 1-3, with more severe phenotypes seen in association with variants in transmembrane domains 1 and 2 and the allosteric binding site between transmembrane domains 2 and 3. Functional analysis of 4 variants in transmembrane domains 1 or 2 (p.Ile246Thr, p.Pro252Leu, p.Ile288Ser, p.Val282Ala) revealed strongly reduced amplitudes of GABA-evoked anionic currents. INTERPRETATION: GABRB2-related epilepsy ranges broadly in severity from genetic generalized epilepsy to developmental and epileptic encephalopathies. Developmental disability and movement disorder are key features. The phenotypic spectrum is comparable to other GABAA receptor-encoding genes. Phenotypic severity varies by protein domain. Experimental evidence supports loss of GABAergic inhibition as the mechanism underlying GABRB2-associated neurodevelopmental disorders. ANN NEUROL 2021;89:573-586.
Assuntos
Epilepsia/fisiopatologia , Transtornos dos Movimentos/fisiopatologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Receptores de GABA-A/genética , Adolescente , Adulto , Animais , Ataxia/genética , Ataxia/fisiopatologia , Atetose/genética , Atetose/fisiopatologia , Criança , Pré-Escolar , Coreia/genética , Coreia/fisiopatologia , Estudos de Coortes , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/fisiopatologia , Distonia/genética , Distonia/fisiopatologia , Epilepsia/genética , Feminino , Genótipo , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/genética , Mutação de Sentido Incorreto , Transtornos do Neurodesenvolvimento/genética , Oócitos , Técnicas de Patch-Clamp , Fenótipo , Domínios Proteicos/genética , Xenopus laevis , Adulto JovemRESUMO
Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.
Assuntos
Hipotireoidismo Congênito , Tosse , Atetose/genética , Coreia , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Humanos , Masculino , Síndrome do Desconforto Respiratório do Recém-Nascido , Fator Nuclear 1 de Tireoide/genéticaRESUMO
RaceRunning enables athletes with limited or no walking ability to propel themselves independently using a three-wheeled frame that has a saddle, handle bars and a chest plate. For RaceRunning to be included as a para athletics event, an evidence-based classification system is required. This study assessed the impact of trunk control and lower limb impairment measures on RaceRunning performance and evaluated whether cluster analysis of these impairment measures produces a valid classification structure for RaceRunning. The Trunk Control Measurement Scale (TCMS), Selective Control Assessment of the Lower Extremity (SCALE), the Australian Spasticity Assessment Scale (ASAS), and knee extension were recorded for 26 RaceRunning athletes. Thirteen male and 13 female athletes aged 24 (SD = 7) years participated. All impairment measures were significantly correlated with performance (rho = 0.55-0.74). Using ASAS, SCALE, TCMS and knee extension as cluster variables in a two-step cluster analysis resulted in two clusters of athletes. Race speed and the impairment measures were significantly different between the clusters (p < 0.001). The findings of this study provide evidence for the utility of the selected impairment measures in an evidence-based classification system for RaceRunning athletes.
Assuntos
Ataxia/classificação , Atetose/classificação , Hipertonia Muscular/classificação , Corrida/classificação , Esportes para Pessoas com Deficiência/classificação , Tronco/fisiopatologia , Adolescente , Adulto , Ataxia/fisiopatologia , Atetose/fisiopatologia , Desempenho Atlético , Lesão Encefálica Crônica/classificação , Lesão Encefálica Crônica/fisiopatologia , Paralisia Cerebral/classificação , Paralisia Cerebral/fisiopatologia , Análise por Conglomerados , Desenho de Equipamento , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Extremidade Inferior/fisiopatologia , Masculino , Hipertonia Muscular/fisiopatologia , Espasticidade Muscular/classificação , Espasticidade Muscular/fisiopatologia , Força Muscular , Amplitude de Movimento Articular/fisiologia , Corrida/fisiologia , Equipamentos Esportivos , Esportes para Pessoas com Deficiência/fisiologia , Adulto JovemRESUMO
The current protocol for classifying Para swimmers with hypertonia, ataxia and athetosis involves a physical assessment where the individual's ability to coordinate their limbs is scored by subjective clinical judgment. The lack of objective measurement renders the current test unsuitable for evidence-based classification. This study evaluated a revised version of the Para swimming assessment for motor coordination, incorporating practical, objective measures of movement smoothness, rhythm error and accuracy. Nineteen Para athletes with hypertonia and 19 non-disabled participants performed 30 s trials of bilateral alternating shoulder flexion-extension at 30 bpm and 120 bpm. Accelerometry was used to quantify movement smoothness; rhythm error and accuracy were obtained from video. Para athletes presented significantly less smooth movement and higher rhythm error than the non-disabled participants (p < 0.05). Random forest algorithm successfully classified 89% of participants with hypertonia during out-of-bag predictions. The most important predictors in classifying participants were movement smoothness at both movement speeds, and rhythm error at 120 bpm. Our results suggest objective measures of movement smoothness and rhythm error included in the current motor coordination test protocols can be used to infer impairment in Para swimmers with hypertonia. Further research is merited to establish the relationship of these measures with swimming performance.
Assuntos
Paralisia Cerebral/fisiopatologia , Hipertonia Muscular/fisiopatologia , Desempenho Psicomotor/fisiologia , Esportes para Pessoas com Deficiência/fisiologia , Natação/fisiologia , Acelerometria , Adulto , Algoritmos , Ataxia/fisiopatologia , Atetose/fisiopatologia , Desempenho Atlético/fisiologia , Fenômenos Biomecânicos/fisiologia , Feminino , Humanos , Masculino , Movimento/fisiologia , Hipertonia Muscular/classificação , Paratletas/classificação , Desempenho Físico Funcional , Amplitude de Movimento Articular/fisiologia , Ombro/fisiologia , Esportes para Pessoas com Deficiência/classificação , Natação/classificação , Gravação em Vídeo , Adulto JovemRESUMO
In general, involuntary movements after stroke are due to a disturbance in the unilateral cortico-basal ganglia loop and appear contralateral to stroke lesions. Crossed involuntary movements after unilateral stroke are very rare. We observed a case of crossed involuntary movements in the left upper limb and right lower limb after a right thalamic hemorrhage expanded to the right subthalamic nucleus. We considered a possible three-step theory as the basis of crossed choreoathetosis. This case informs our better understanding of the cortico-basal ganglia loop and involuntary movements after stroke.
Assuntos
Atetose/etiologia , Coreia/etiologia , Acidente Vascular Cerebral Hemorrágico/complicações , Movimento , Tálamo/irrigação sanguínea , Idoso de 80 Anos ou mais , Atetose/diagnóstico , Atetose/fisiopatologia , Coreia/diagnóstico , Coreia/fisiopatologia , Acidente Vascular Cerebral Hemorrágico/diagnóstico por imagem , Humanos , MasculinoRESUMO
BACKGROUND: The expression of the NKX2-1 gene and its encoded protein, thyroid transcription factor 1 (TTF-1), plays a role in pulmonary surfactant homeostasis and lung development. NKX2-1 mutations have been associated with neonatal respiratory distress, hypotonia, choreoathetosis and congenital hypothyroidism. These clinical findings have been coined brain-lung-thyroid syndrome, although not all three organs are always involved. While many of these children develop interstitial lung disease, no systematic review of chest high-resolution CT (HRCT) findings has been reported. OBJECTIVE: To summarize the clinical presentations, pathology and HRCT imaging findings of children with NKX2-1 mutations. MATERIALS AND METHODS: We identified six children with NKX2-1 mutations, deletions or duplications confirmed via genetic testing at our institution. Three pediatric radiologists reviewed the children's HRCT imaging findings and ranked the dominant findings in order of prevalence via consensus. We then correlated the imaging findings with histopathology and clinical course. RESULTS: All children in the study were heterozygous for NKX2-1 mutations, deletions or duplications. Ground-glass opacities were the most common imaging feature, present in all but one child. Consolidation was also a prevalent finding in 4/6 of the children. Architectural distortion was less common. CONCLUSION: HRCT findings of TTF-1 deficiency are heterogeneous and evolve over time. There is significant overlap between the HRCT findings of TTF-1 deficiency, other surfactant dysfunction mutations, and pulmonary interstitial glycogenosis. TTF-1 deficiency should be considered in term infants presenting with interstitial lung disease, especially if hypotonia or hypothyroidism is present.
Assuntos
Atetose/diagnóstico por imagem , Atetose/genética , Coreia/diagnóstico por imagem , Coreia/genética , Hipotireoidismo Congênito/diagnóstico por imagem , Hipotireoidismo Congênito/genética , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Fator Nuclear 1 de Tireoide/genética , Tomografia Computadorizada por Raios X/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Fator Nuclear 1 de Tireoide/deficiênciaRESUMO
AIM: To identify and systematically review the psychometric properties and clinical utility of dystonia and choreoathetosis scales reported for children with cerebral palsy (CP). METHOD: Six electronic databases were searched for dystonia and choreoathetosis scales with original psychometric data for children with CP aged 0 to 18 years. RESULTS: Thirty-four papers met the inclusion criteria, which contained six scales purported to measure dystonia and/or choreoathetosis in children with CP: the Burke-Fahn-Marsden Dystonia Rating Scale; Barry-Albright Dystonia Scale; Unified Dystonia Rating Scale; Movement Disorder-Childhood Rating Scale; Movement Disorder-Childhood Rating Scale 0-3 Years; and the Dyskinesia Impairment Scale. INTERPRETATION: Each scale provides useful information about dyskinesia, with most focusing on dystonia. The Barry-Albright Dystonia Scale, which was designed for CP, is the most commonly reported scale and least complex to use clinically. The Dyskinesia Impairment Scale is the only tool to consider both dystonia and choreoathetosis in CP. All tools are designed to classify movement disorders at the level of body functions and structures, rather than activity limitations or participation restrictions, although many provide some insight into the impact of dystonia on activities. Further studies are required to fully examine the validity, reliability, responsiveness, and clinical utility of each scale specifically for children with CP.
Assuntos
Atetose/diagnóstico , Paralisia Cerebral/diagnóstico , Coreia/diagnóstico , Distúrbios Distônicos/diagnóstico , Índice de Gravidade de Doença , Adolescente , Atetose/etiologia , Paralisia Cerebral/complicações , Criança , Pré-Escolar , Coreia/etiologia , Distúrbios Distônicos/etiologia , Humanos , LactenteAssuntos
Atetose/genética , Coreia/genética , Hipotireoidismo Congênito/genética , Mutação/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Fator Nuclear 1 de Tireoide/genética , Adulto , Idoso , Sequência de Aminoácidos , Linhagem Celular Tumoral , Criança , Feminino , Células HeLa , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Alternating hemiplegia of childhood (AHC) is a rare neurological disorder that manifests recurrent attacks of hemiplegia, oculogyric, and choreoathetotic involuntary movements. De novo mutations in ATP1A3 cause three types of neurological diseases: AHC; rapid-onset dystonia-Parkinsonism (RDP); and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndromes. It remains to be determined whether or not a rare mutation in ATP1A3 may cause atypical phenotypes. CASE PRESENTATION: A 7-year-old boy presented with recurrent symptoms of generalized paralysis since 1 year and 5 months of age. Hypotonia, dystonia, and choreoathetosis persisted with exacerbation under febrile conditions, but no cerebellar ataxia had ever evolved in 6 years. Whole-exome sequencing (WES) was performed to determine his genetic background, and mutations were validated by the Sanger method. Crude protein extracts were prepared from the cultured cells, and expression of the wild-type or mutant ATP1A3 proteins were analyzed by Western blotting. WES identified a de novo pathogenic mutation in ATP1A3 (c.2266C > T:p.R756C) for this patient. A literature overview of two reported cases with p.R756C and p.R756H mutations showed both overlapping and distinct phenotypes when compared with those of the present case. The expression of the mutant form (R756C) of ATP1A3 did not differ markedly from that of the wild-type and D801N proteins. CONCLUSIONS: This study confirmed that p.R756C mutation of ATP1A3 cause atypical forms of AHC-associated disorders. The wide spectra of neurological phenotypes in AHC are linked to as-yet-unknown deficits in the functions of mutant ATP1A3.
Assuntos
Atetose/complicações , Atetose/genética , Coreia/genética , Hemiplegia/complicações , Hemiplegia/genética , Paralisia/genética , ATPase Trocadora de Sódio-Potássio/genética , Criança , Coreia/complicações , Humanos , Masculino , Mutação , Paralisia/complicações , FenótipoRESUMO
AIM: The aim of the study was to map clinical patterns of dystonia and choreoathetosis and to assess the relation between functional classifications and basal ganglia and thalamus lesions in participants with dyskinetic cerebral palsy (CP). METHODS: In this cross-sectional study, 55 participants with dyskinetic CP (mean age 14y 6mo, SD 4y 1mo; range 6-22y) were assessed with the Dyskinesia Impairment Scale and classified with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS). RESULTS: Dystonia and choreoathetosis are simultaneously present. Median levels of dystonia (70.2%) were significantly higher than levels of choreoathetosis (26.7%) and both were significantly higher during activity than at rest (both p<0.01). High correlations were found between dystonia levels and GMFCS level (Spearman's rank correlation coefficient, rS =0.70; 95% confidence interval [CI] 0.53-0.81; p<0.01) and MACS (rS =0.65; 95% CI 0.47-0.81; p<0.01), and fair correlation with CFCS (rs =0.36; 95% CI=0.11-0.57; p<0.05). No significant correlation was found between choreoathetosis levels and motor classifications. Finally, higher choreoathetosis levels were found in participants with pure thalamus and basal ganglia lesions (p=0.03) than mixed lesions, but not for dystonia (p=0.41). INTERPRETATION: Dystonia and choreoathetosis increase during activity. However, dystonia predominates and seems to have a larger impact on functional abilities. Our findings further suggest that choreoathetosis seems to be more linked to pure thalamus and basal ganglia lesions than dystonia.
Assuntos
Atetose/fisiopatologia , Paralisia Cerebral/fisiopatologia , Coreia/fisiopatologia , Distonia/fisiopatologia , Adolescente , Adulto , Atetose/epidemiologia , Atetose/etiologia , Doenças dos Gânglios da Base/patologia , Paralisia Cerebral/complicações , Paralisia Cerebral/epidemiologia , Criança , Coreia/epidemiologia , Coreia/etiologia , Estudos Transversais , Distonia/epidemiologia , Distonia/etiologia , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Tálamo/patologia , Adulto JovemRESUMO
PURPOSE: Nitrous oxide (N2O) is neurotoxic by interfering with vitamin B12 bioavailability. The clinical picture is indistinguishable to that of subacute combined degeneration (SCD). A movement disorder might occur though it is not a characteristic feature. We report a patient with N2O-induced SCD, exhibiting a combination of different involuntary movements. CASE REPORT: A 20-year-old woman presented with one month of progressive unsteady gait, involuntary movements and tingling sensation in a stocking-glove distribution. She had used N2O and ketamine intermittently for recreational purposes for about two years. Neurological examination demonstrated normal cranial nerve functions except for dystonia in the facial muscle and tongue. Her muscle strength was full, but there were bilateral hyperreflexia and extensor plantar response. She exhibited dystonia in four limbs with athetoid movement in fingers and toes, worsened by eye closure. Vibration and proprioception were impaired. Laboratory tests revealed anemia (Hb: 9.9 g/dl) with normal mean corpuscular volume (85.7 fL) and decreased iron level (22 µg/dl) while other results were normal including serum vitamin B12 level (626 pg/ml). Magnetic resonance imaging showed a hyperintense lesion from C1 to C6 level in the posterior column. She was diagnosed as having SCD caused by N2O abuse, presenting with generalized dystonia and pseudoathetosis. The involuntary movements disappeared with vitamin B12 supplementation. CONCLUSION: Movement disorders may be the rare manifestations of SCD associated with N2O abuse. Early recognition of the etiology is vital because it is treatable with vitamin B12 and methionine.
Assuntos
Atetose/induzido quimicamente , Distonia/induzido quimicamente , Transtornos Neurológicos da Marcha/induzido quimicamente , Óxido Nitroso/toxicidade , Degeneração Combinada Subaguda/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Atetose/tratamento farmacológico , Distonia/tratamento farmacológico , Feminino , Transtornos Neurológicos da Marcha/tratamento farmacológico , Humanos , Degeneração Combinada Subaguda/tratamento farmacológico , Vitamina B 12/administração & dosagem , Vitamina B 12/farmacologia , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/farmacologia , Adulto JovemRESUMO
Benign familial infantile epilepsy (BFIE) is a self-limited seizure disorder that occurs in infancy and has autosomal-dominant inheritance. We have identified heterozygous mutations in PRRT2, which encodes proline-rich transmembrane protein 2, in 14 of 17 families (82%) affected by BFIE, indicating that PRRT2 mutations are the most frequent cause of this disorder. We also report PRRT2 mutations in five of six (83%) families affected by infantile convulsions and choreoathetosis (ICCA) syndrome, a familial syndrome in which infantile seizures and an adolescent-onset movement disorder, paroxysmal kinesigenic choreoathetosis (PKC), co-occur. These findings show that mutations in PRRT2 cause both epilepsy and a movement disorder. Furthermore, PRRT2 mutations elicit pleiotropy in terms of both age of expression (infancy versus later childhood) and anatomical substrate (cortex versus basal ganglia).
Assuntos
Atetose/genética , Coreia/genética , Epilepsia Neonatal Benigna/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Convulsões/genética , Idade de Início , Animais , Sequência de Bases , Encéfalo/patologia , Pré-Escolar , Cromossomos Humanos Par 16/genética , Humanos , Lactente , Masculino , Camundongos , Dados de Sequência Molecular , Mutação , LinhagemRESUMO
Prior work has highlighted the challenges faced by people with athetosis when trying to acquire on-screen targets using a mouse or trackball. The difficulty of positioning the mouse cursor within a confined area has been identified as a challenging task. We have developed a target acquisition assistance algorithm that features transition assistance via directional gain variation based on target prediction, settling assistance via gain reduction in the vicinity of a predicted target, and expansion of the predicted target as the cursor approaches it. We evaluated the algorithm on improving target acquisition efficiency among seven participants with athetoid cerebral palsy. Our results showed that the algorithm significantly reduced the overall movement time by about 20%. Considering the target acquisition occurs countless times in the course of regular computer use, the accumulative effect of such improvements can be significant for improving the efficiency of computer interaction among people with athetosis.
Assuntos
Algoritmos , Atetose/fisiopatologia , Atetose/reabilitação , Software , Análise e Desempenho de Tarefas , Processamento de Texto , Periféricos de Computador , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Mutations of the SCN2A gene have originally been described in association with benign familial neonatal-infantile seizures (BFNIS). Recently, single patients with more severe phenotypes and persisting epileptic encephalopathies have been recognized. We report the case of a girl with severe infantile onset epileptic encephalopathy and a de novo missense mutation in the SCN2A gene (c.4025T > C/ = ; p.L1342P/ = ), who presented with a transient choreatic movement disorder, hypersomnia, and progressive brain atrophy. Whole exome sequencing did not reveal any other disease causing mutation. Our patient contributes to the expanding phenotypic spectrum of SCN2A-related disorders and underlines the importance of genetic workup in epileptic encephalopathies.
Assuntos
Atetose/genética , Coreia/genética , Distúrbios do Sono por Sonolência Excessiva/genética , Epilepsia/diagnóstico , Epilepsia/genética , Mutação de Sentido Incorreto , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Encéfalo/fisiopatologia , Feminino , Humanos , LactenteRESUMO
"Bath salts" is a well known street drug which can cause several cardiovascular and neuropsychiatric symptoms. However, only one case of acute kidney injury has been reported in the literature. We present a case with sympathomimetic syndrome, choreoathetosis, gustatory and olfactory hallucinations, and acute kidney injury following the use of bath salts. A 37-year-old man with past medical history of hypertension and depression was brought to the emergency center with body shaking. Three days before admission he injected 3 doses of bath salts intravenously and felt eye pain with blurry vision followed by a metallic taste, strange smells, profuse sweating, and body shaking. At presentation he had a sympathomimetic syndrome including high blood pressure, tachycardia, tachypnea, and hyperhydrosis with choreoathetotic movements. Laboratory testing revealed leukocytosis and acute kidney injury with a BUN of 95 mg/ dL and a creatinine of 15.2 mg/dL. Creatine kinase was 4,457 IU/dL. Urine drug screen is negative for amphetamine, cannabinoids, and cocaine; blood alcohol level was zero. During his ICU stay he became disoriented and agitated. Supportive treatment with 7.2 liters of intravenous fluid over 3 days, haloperidol, and lorazepam gradually improved his symptoms and his renal failure. Bath salts contain 3,4-methylenedioxypyrovalerone, a psychoactive norepinephrine and dopamine reuptake inhibitor. Choreoathetosis in this patient could be explained through dopaminergic effect of bath salts or uremic encephalopathy. The mechanism for acute kidney injury from bath salts may involve direct drug effects though norepinephrine and dopamine-induced vasoconstriction (renal ischemia), rhabdomyolysis, hyperthermia, and/or volume contraction.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Atetose/induzido quimicamente , Benzodioxóis/intoxicação , Catecolaminas/intoxicação , Estimulantes do Sistema Nervoso Central/intoxicação , Coreia/induzido quimicamente , Metanfetamina/análogos & derivados , Pirrolidinas/intoxicação , Adulto , Drogas Desenhadas/intoxicação , Humanos , Injeções , Masculino , Metanfetamina/intoxicação , Síndrome , Catinona SintéticaAssuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Diagnóstico Diferencial , Encefalite/diagnóstico , Soropositividade para HIV/diagnóstico , Adolescente , Agressão , Atetose/etiologia , Coreia/etiologia , Discinesias/etiologia , Encefalite/etiologia , Encefalite/fisiopatologia , Exantema/etiologia , Febre/etiologia , Escala de Coma de Glasgow , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/fisiopatologia , Soropositividade para HIV/complicações , Soropositividade para HIV/fisiopatologia , Humanos , Humor Irritável , Imageamento por Ressonância Magnética , Masculino , Hipertonia Muscular/etiologia , Piloereção , Transtornos Psicóticos/etiologia , Reflexo Anormal , Convulsões/etiologia , Taquicardia/etiologiaRESUMO
PURPOSE: This case report describes the physical therapy examination, intervention, and outcomes for a 5-year-old girl who developed choreoathetosis following mitral valve repair. CASE DESCRIPTION: This child was admitted to an inpatient short-term rehabilitation program with marked choreoathetosis and dependence for all functional mobility. She received physical therapy twice a day for 5 weeks. Physical therapy intervention included therapeutic exercise emphasizing stabilization and closed chain exercises, aquatic therapy, and functional training to improve gross motor skills and mobility. Tests and measures included the Selective Control Assessment of the Lower Extremity, 66-item Gross Motor Function Measure, and Pediatric Evaluation of Disability Inventory. OUTCOMES: At discharge, this child demonstrated improvements in her Selective Control Assessment of the Lower Extremity, Gross Motor Function Measure, and Pediatric Evaluation of Disability Inventory scores. She was independent in all functional mobility tasks. SUMMARY: This case study describes physical therapy tests and measures, intervention, and positive outcomes for a child with sudden-onset choreoathetosis.
Assuntos
Atetose/reabilitação , Coreia/reabilitação , Crianças com Deficiência/reabilitação , Modalidades de Fisioterapia , Pré-Escolar , Avaliação da Deficiência , Feminino , Humanos , Destreza MotoraRESUMO
BACKGROUND: Movement disorders in children and adolescents with dyskinetic cerebral palsy (CP) are commonly assessed from video recordings, however scoring is time-consuming and expert knowledge is required for an appropriate assessment. OBJECTIVE: To explore a machine learning approach for automated classification of amplitude and duration of distal leg dystonia and choreoathetosis within short video sequences. METHODS: Available videos of a heel-toe tapping task were preprocessed to optimize key point extraction using markerless motion analysis. Postprocessed key point data were passed to a time series classification ensemble algorithm to classify dystonia and choreoathetosis duration and amplitude classes (scores 0, 1, 2, 3, and 4), respectively. As ground truth clinical scoring of dystonia and choreoathetosis by the Dyskinesia Impairment Scale was used. Multiclass performance metrics as well as metrics for summarized scores: absence (score 0) and presence (score 1-4) were determined. RESULTS: Thirty-three participants were included: 29 with dyskinetic CP and 4 typically developing, age 14 years:6 months ± 5 years:15 months. The multiclass accuracy results for dystonia were 77% for duration and 68% for amplitude; for choreoathetosis 30% for duration and 38% for amplitude. The metrics for score 0 versus score 1 to 4 revealed an accuracy of 81% for dystonia duration, 77% for dystonia amplitude, 53% for choreoathetosis duration and amplitude. CONCLUSIONS: This methodology study yielded encouraging results in distinguishing between presence and absence of dystonia, but not for choreoathetosis. A larger dataset is required for models to accurately represent distinct classes/scores. This study presents a novel methodology of automated assessment of movement disorders solely from video data.
Assuntos
Atetose , Paralisia Cerebral , Distonia , Gravação em Vídeo , Humanos , Adolescente , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/complicações , Paralisia Cerebral/classificação , Paralisia Cerebral/diagnóstico , Masculino , Feminino , Criança , Distonia/fisiopatologia , Distonia/diagnóstico , Distonia/classificação , Distonia/etiologia , Atetose/fisiopatologia , Atetose/diagnóstico , Atetose/etiologia , Extremidade Inferior/fisiopatologia , Aprendizado de MáquinaRESUMO
Background: Brain-lung-thyroid syndrome (BLTS) is caused by NKX2-1 haploinsufficiency, resulting in chorea/choreoathetosis, respiratory problems, and hypothyroidism. Genes interacting with NKX2-1 mutants influence its phenotypic variability. We report a novel NKX2-1 missense variant and the modifier function of TAZ/WWTR1 in BLTS. Methods: A child with BLTS underwent next-generation sequencing panel testing for thyroid disorders. His family was genotyped for NKX2-1 variants and screened for germline mosaicism. Mutant NKX2-1 was generated, and transactivation assays were performed on three NKX2-1 target gene promoters. DNA binding capacity and protein-protein interaction were analyzed. Results: The patient had severe BLTS and carried a novel missense variant c.632A>G (p.N211S) in NKX2-1, which failed to bind to specific DNA promoters, reducing their transactivation. TAZ cotransfection did not significantly increase transcription of these genes, although the variant retained its ability to bind to TAZ. Conclusions: We identify a novel pathogenic NKX2-1 variant that causes severe BLTS and is inherited through germline mosaicism. The mutant lacks DNA-binding capacity, impairing transactivation and suggesting that NKX2-1 binding to DNA is essential for TAZ-mediated transcriptional rescue.