RESUMO
The mitochondrial deoxyribonucleotide (dNTP) pool is separated from the cytosolic pool because the mitochondria inner membrane is impermeable to charged molecules. The mitochondrial pool is maintained by either import of cytosolic dNTPs through dedicated transporters or by salvaging deoxynucleosides within the mitochondria; apparently, enzymes of the de novo dNTP synthesis pathway are not present in the mitochondria. In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on the mitochondrial salvage pathway enzymes, the deoxyribonucleosides kinases. Two of the four human deoxyribonucleoside kinases, deoxyguanosine kinase (dGK) and thymidine kinase-2 (TK2), are expressed in mitochondria. Human dGK efficiently phosphorylates deoxyguanosine and deoxyadenosine, whereas TK2 phosphorylates deoxythymidine, deoxycytidine and deoxyuridine. Here we identify two mutations in TK2, histidine 90 to asparagine and isoleucine 181 to asparagine, in four individuals who developed devastating myopathy and depletion of muscular mitochondrial DNA in infancy. In these individuals, the activity of TK2 in muscle mitochondria is reduced to 14-45% of the mean value in healthy control individuals. Mutations in TK2 represent a new etiology for mitochondrial DNA depletion, underscoring the importance of the mitochondrial dNTP pool in the pathogenesis of mitochondrial depletion.
Assuntos
DNA Mitocondrial/metabolismo , Mitocôndrias Musculares/enzimologia , Miopatias Mitocondriais/genética , Mutação Puntual/genética , Timidina Quinase/genética , Sequência de Bases , Pré-Escolar , Análise Mutacional de DNA , DNA Mitocondrial/genética , Feminino , Humanos , Lactente , Masculino , Mitocôndrias Musculares/genética , Mitocôndrias Musculares/patologia , Miopatias Mitocondriais/enzimologia , Miopatias Mitocondriais/patologia , Miopatias Mitocondriais/fisiopatologia , Dados de Sequência Molecular , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Timidina Quinase/metabolismoRESUMO
BACKGROUND: Peritoneal Cancer Index (PCI) and complete cytoreduction are the best outcome predictors following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Lesions in critical areas, regardless of PCI, complicate surgery and impact oncological outcomes. We prospectively defined "Critical lesions" (CL) as penetrating the hepatic hilum, diaphragm at hepatic outflow, major blood vessels, pancreas, or urinary tract. METHODS: Retrospective analysis of a prospective database of 352 CRS + HIPEC patients from 2015 to 2019. Excluded patients with aborted/redo operation (n = 112), or incomplete data (n = 19). Patients categorized by CL status and compared: operative time, estimated blood loss (EBL), PCI, transfusions, hospital stay, post-operative complications and mortality, overall survival (OS) and disease-free survival (DFS). RESULTS: Included 221 patients (78 CL; 143 no-CL). No difference in patients' characteristics: age, BMI, gender or co-morbidities noted. Operative time longer (5.3 h vs 4.3 h, p < 0.01), EBL higher (769 ml vs 405 ml, p < 0.01), transfusions higher (1.9 vs 0.7 Units, p < 0.001) and PCI higher (15.5 vs 9.5, p < 0.01) in CL. No difference in major complications. Postoperative complications, CL, OR-time and transfusions were predictive of OS in univariate analysis, while only complications remained on multivariate analysis. Median follow up of 21.4 months, 3-year DFS/OS was 22% vs 30% (p < 0.037) and 73% vs 87% (p < 0.014) in CL and non-CL, respectively. Despite CL complete resection, 17/38 patients (44.7%) that recurred had recurrence at previous CL site. CONCLUSIONS: Critical lesions complicate surgery and may be associated with poor oncological outcomes with high local recurrence rate, despite no significant difference in complications. Utilizing adjuvant or intra-operative radiation may be beneficial.
Assuntos
Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Invasividade Neoplásica/patologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Transfusão de Sangue/estatística & dados numéricos , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: Long-term follow-up of children with idiopathic West syndrome (WS) treated with adrenocorticotropic hormone (ACTH) or vigabatrin. METHODS: Records of 28 normal magnetic resonance imaging (MRI) WS cases were reviewed for seizure development and cognitive outcome in relation to treatment type and lag. RESULTS: Average age at disease onset was 5.5 months, and average lag time to treatment was 25 days. Fourteen patients were treated with ACTH (eight early and six late), and 14 with vigabatrin (without delay). Response rates were 88% for ACTH and 80% for vigabatrin. Short-term outcomes for seizure cessation and electroencephalography normalization were identical between the groups. In the long-term, early ACTH treatment was better than the rest combined. Average follow-up time was 9 years. A normal cognitive outcome was achieved in 100% of the early-ACTH group, 67% of the late-ACTH group and 54% of the vigabatrin group (P = 0.03). Seizures subsequently developed in 54% of the vigabatrin group, in 33% of the late ACTH group, and 0% of the early ACTH group (P < 0.05). CONCLUSIONS: Idiopathic WS with normal MRI is associated with a good cognitive outcome. Early ACTH treatment, administered within 1 month, yields a better cognitive and seizure outcome than vigabatrin or late ACTH.
Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Anticonvulsivantes/uso terapêutico , Desenvolvimento Infantil/efeitos dos fármacos , Espasmos Infantis/tratamento farmacológico , Vigabatrina/uso terapêutico , Adolescente , Idade de Início , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Cognição/efeitos dos fármacos , Eletroencefalografia , Feminino , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Convulsões/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: There is interest in using animal-mounted sensors to provide the detailed timeline of domesticated ruminant behaviour on rangelands. NEW METHOD: Working with beef cattle, we evaluated the pedometer-like IceTag device (IceRobotics, Edinburgh, Scotland) that records step events, leg movement and body position (upright versus lying). We used partition analysis to compare behaviour as inferred from the device data with true behaviour as coded at high resolution from carefully synchronized video observations of 5-min duration. RESULTS: Malfunctions reduced the target dataset by 7%. The correspondence between IceTag and video-coded step counts was excellent (r2=0.97), and the device's indications of upright or lying corresponded well (error rate=1.4%) to the video-coded values. However, the proportion of steps that could be matched individually was relatively low (65% at a tolerance of 0.5s), and the indicated start of a lying bout was often triggered by leg movements of an upright animal. Partition analysis of Grazing versus Not-Grazing yielded an overall error rate of 22%. In both three- and four-way classifications of behaviour (Graze, Rest, Travel; Graze, Stand, Lie, Travel) error rates were low for non-graze behaviours, but only 25% of Graze observations were correctly classified; the overall error rate was 22%. COMPARISON WITH EXISTING METHOD(S): The IceTag device performed well in mapping the diurnal patterns of animal position and step rate, but less well in separating grazing from upright resting. CONCLUSIONS: Our results suggest that pedometry is not the ideal method for classifying behaviour when grazing is of paramount interest.
Assuntos
Comportamento Animal/fisiologia , Monitorização Ambulatorial/instrumentação , Postura/fisiologia , Dispositivos Eletrônicos Vestíveis/normas , Animais , Bovinos , Fazendas , Feminino , Herbivoria/fisiologia , Gado , Monitorização Ambulatorial/métodos , Monitorização Ambulatorial/normas , GravidezRESUMO
Strains carrying a marked Ty element (TyUra) in the LYS2 locus were transformed with plasmids bearing a differently marked Ty1 element (Ty1Neo) under the control of the GAL promoter. When these strains were grown in glucose, a low level of gene conversion events involving TyUra was detected. Upon growth on galactose an increase in the rate of gene conversion was seen. This homologous recombination is not the consequence of increased levels of transposition. When an intron-containing fragment was inserted into Ty1Neo, some of the convertants had the intron removed, implying an RNA intermediate. Mutations that affect reverse transcriptase or reverse transcription of Ty1Neo greatly reduce the induction of recombination in galactose. Thus, Ty cDNA is involved in homologous gene conversion with chromosomal copies of Ty elements. Our results have implications about the way families of repeated sequences retain homogeneity throughout evolution.
Assuntos
DNA de Cadeia Simples/metabolismo , Conversão Gênica , Sequências Repetitivas de Ácido Nucleico/genética , Saccharomyces cerevisiae/genética , Evolução Biológica , DNA Recombinante , Marcadores Genéticos/genética , Regiões Promotoras Genéticas , RNA/metabolismo , DNA Polimerase Dirigida por RNA/metabolismo , Transcrição GênicaRESUMO
Inflammation and fibrosis are well-defined mechanisms involved in the pathogenesis of the incurable Laminin α2-deficient congenital muscular dystrophy (MDC1A), while apoptosis mechanism is barely discussed. Our previous study showed treatment with Losartan, an angiotensin II type I receptor antagonist, improved muscle strength and reduced fibrosis through transforming growth factor beta (TGF-ß) and mitogen-activated protein kinases (MAPK) signaling inhibition in the dy(2J)/dy(2J) mouse model of MDC1A. Here we show for the first time that Losartan treatment up-regulates and shifts the nuclear factor kappa B (NFκB) signaling pathway to favor survival versus apoptosis/damage in this animal model. Losartan treatment was associated with significantly increased serum tumor necrosis factor alpha (TNF-α) level, p65 nuclei accumulation, and decreased muscle IκB-ß protein level, indicating NFκB activation. Moreover, NFκB anti-apoptotic target genes TNF receptor-associated factor 1 (TRAF1), TNF receptor-associated factor 2 (TRAF2), cellular inhibitor of apoptosis (cIAP2), and Ferritin heavy chain (FTH1) were increased following Losartan treatment. Losartan induced protein expression toward a pro-survival profile as BCL-2 expression levels were increased and Caspase-3 expression levels were decreased. Muscle apoptosis reduction was further confirmed using terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay. Thus, along with TGF-ß and MAPK signaling, NFκB serves as an important regulatory pathway which following Losartan treatment promotes survival in the dy(2J)/dy(2J) mouse model of MDC1A.
Assuntos
Distrofias Musculares/genética , NF-kappa B/genética , Fator 1 Associado a Receptor de TNF/biossíntese , Fator 2 Associado a Receptor de TNF/biossíntese , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Modelos Animais de Doenças , Ferritinas/biossíntese , Humanos , Proteínas Inibidoras de Apoptose/biossíntese , Losartan/administração & dosagem , Camundongos , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofias Musculares/tratamento farmacológico , Distrofias Musculares/patologia , Transdução de Sinais , Fator 1 Associado a Receptor de TNF/genética , Fator 2 Associado a Receptor de TNF/genética , Fator de Transcrição RelA/metabolismoRESUMO
Emery-Dreifuss Muscular Dystrophy (EMD or EDMD) is a rare X-linked recessive disorder, characterized by progressive muscle wasting and weakness, contractures, and cardiomyopathy, manifesting as heart block. Mutation analysis at the EMD gene locus was performed in 4 unrelated Israeli families with X-linked EMD and in one sporadic case. In the 4 families 4 different mutations were found, 3 of which were novel. These included two frame shift mutations in exon 2 (333delT and 412insA) and one base pair substitution at the consensus +1 donor splice in intron 5 (1429G-->A). The fourth mutation in exon 6 (1675-1678delTCCG) has been previously described. No mutations were identified in the one sporadic case. Two of the three novel mutations were found in exon 2. A summary of the previously published mutations described in the EMD Mutation Database (http://www.path.cam.ac.uk/emd/) as well as the mutations described in our study suggest that the distribution of mutations in EMD gene is not entirely random and that exon 2 is prone to mutations. Hum Mutat 17:522, 2001.
Assuntos
Proteínas de Membrana/genética , Distrofia Muscular de Emery-Dreifuss/genética , Timopoietinas/genética , Sequência de Bases , DNA/química , DNA/genética , Análise Mutacional de DNA , Saúde da Família , Feminino , Humanos , Israel , Masculino , Mutagênese Insercional , Mutação , Proteínas Nucleares , Deleção de SequênciaRESUMO
Chronic inflammatory demyelinating neuropathy (CIDP) is a rare disease in childhood. We reviewed the clinical characteristics, response to therapy, and long-term prognosis in 13 children (1.5 to 16 years of age) diagnosed with CIDP at Washington University Medical Center, St. Louis, and the Royal Children's Hospital, Melbourne, Australia, between 1979 and 1994. The most common presenting symptom (in 11/13 [85%]) was lower extremity weakness associated with difficulty in walking. Preceding events within 1 months of onset, mostly intercurrent infections or vaccinations, occurred in seven children (54%). The disease was monophasic in three children (23%). One relapse occurred in four (30%) and multiple relapses in six (46%). All patients had at least short-term response to steroids. Three children (23%) recovered completely during the first year. Ten children (77%) had residual weakness after an average follow-up of 6 years. There seems to be two populations of children with CIDP. One subgroup, with a favorable prognosis, progressed to peak disability over less than 3 months; these children often have a monophasic course with complete resolution of symptoms and signs and withdrawal from all medications by 1 year after onset. A second subgroup progressed for 3 months or longer; these children all required substantial does of prednisone for prolonged periods and had considerable long-term morbidity with persistent weakness.
Assuntos
Doenças Desmielinizantes/fisiopatologia , Adolescente , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Humanos , Lactente , Inflamação , Masculino , Tempo de Reação/fisiologia , Fatores de TempoRESUMO
We have studied changes in energy expenditure and body composition in adult males with Emery-Dreifuss muscular dystrophy, age-matched males with hyperCKemia and age-matched healthy controls. All participants were studied twice, 2-3 years apart. Resting energy expenditure was studied by indirect calorimetry, lean body mass and body fat by dual X-ray absorptiometry, and muscle mass was estimated based on 24-h urinary creatinine excretion. At baseline and 2-3 years later, body fat was significantly higher (P < 0.011 and P < 0.003, respectively) and lean body mass significantly lower (P < 0.024 and P < 0.012, respectively) in patients with Emery-Dreifuss muscular dystrophy as compared to subjects with hyperCKemia and healthy controls. Resting energy expenditure, over the study period, increased significantly in patients with Emery-Dreifuss muscular dystrophy (P < 0.031), but not in patients with hyperCKemia nor in healthy controls. Our study suggests that patients with Emery-Dreifuss muscular dystrophy may have increased energy expenditure relative to healthy subjects. If not met by increased caloric intake, this greater energy expenditure may partially contribute to a further deterioration in their muscle performance.
Assuntos
Metabolismo Energético/genética , Músculo Esquelético/metabolismo , Distrofia Muscular de Emery-Dreifuss/metabolismo , Descanso , Regulação para Cima/genética , Absorciometria de Fóton , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Adulto , Atrofia/metabolismo , Atrofia/patologia , Atrofia/fisiopatologia , Índice de Massa Corporal , Creatinina/urina , Humanos , Hipercalcemia/metabolismo , Hipercalcemia/fisiopatologia , Hiperpotassemia/metabolismo , Hiperpotassemia/fisiopatologia , Estudos Longitudinais , Masculino , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Emery-Dreifuss/patologia , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Valores de Referência , Descanso/fisiologiaRESUMO
We describe two brothers with clinical and histological findings of type 2 spinal muscular atrophy (SMA) associated with small head circumference (<2%) and normal cognitive development. No survival motor neuron (SMN) or neuronal apoptosis-inhibitory protein (NAIP) deletions were detected in these sibs, and they were discordant for the haplotypes determined by DNA markers flanking the 5q13 SMA locus. These findings support the presence of a distinct anterior horn disease unrelated to 5q13. This entity may have either autosomal recessive or X-linked inheritance.
Assuntos
Atrofia Muscular Espinal/genética , Pré-Escolar , Cromossomos Humanos Par 5 , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Deleção de Genes , Marcadores Genéticos , Haplótipos , Humanos , Inteligência , Masculino , Atrofia Muscular Espinal/classificação , Atrofia Muscular Espinal/patologia , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/genética , Proteína Inibidora de Apoptose Neuronal , Proteínas de Ligação a RNA , Proteínas do Complexo SMNRESUMO
Flumazenil (Flu) (Ro 15-1788, Anexate) is a newly synthetized specific benzodiazepine (BZD) antagonist which was recently introduced for clinical study. The drug was intravenously injected, in titrated doses, to patients undergoing diagnostic or therapeutic procedures in order to reverse the sedative effects of BZDs. A total of 63 patients undergoing hand surgery under i.v. regional block, lower abdominal surgery under epidural anesthesia, cardiac catheterization, intracardiac catheter ablation, cardioversion, gastroscopy and bronchoscopy were studied. Flu in a dose ranging from 0.1 to 0.42 mg effectively reversed BZD-induced sedation in all patients 1-2 min following i.v. injection. Patients were fully awake and oriented yet calm and in good mood. Flu was well tolerated even in the high risk cardiac patients, with no significant changes in vital signs nor any sign of local irritation at the site of Flu injection. No significant resedation was observed. Thus Flu was very useful in reversing BZD-induced sedation or unconsciousness in a variety of clinical situations.
Assuntos
Ansiolíticos/antagonistas & inibidores , Flumazenil/uso terapêutico , Idoso , Broncoscopia , Cateterismo Cardíaco , Método Duplo-Cego , Cardioversão Elétrica , Feminino , Gastroscopia , Hemodinâmica/efeitos dos fármacos , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Período Pós-Operatório , Distribuição AleatóriaRESUMO
ICU patients often require sedation. Midazolam (M), a new imidazobenzodiazepine, features rapid onset and rapid elimination time. Flumazenil (Ro 15-1788) is a new benzodiazepine antagonist. We studied the efficacy and safety of M by continuous infusion in 28 ICU patients: 16 post major surgery, and 12 medical patients, aged 20-77 years. M was administered as a loading dose of 0.05-0.15 mg/kg per min followed by continuous infusion of 0.05-0.1 mg/kg per h titrated to maintain patients asleep but arousable. M was administered for up to 14 days in doses of 1-15 mg/h and cumulative doses of up to 1915 mg. No untoward effects were noted except for slight decreases in blood pressure following the loading dose. ACTH challenge tests performed before and 24 h or more following the start of M showed no depression of adrenal responsivity. All patients meeting weaning criteria were weaned off mechanical ventilation while still on M. In 13 patients extubation was performed immediately after M was stopped, and flumazenil (0.38 +/- 0.27 mg, i.v.) given until full awakening. Patients remained awake yet calm. Vital signs remained stable after flumazenil. Midazolam by continuous infusion appears to be a safe and effective mode of sedation in ICU patients. Flumazenil may increase the flexibility and safety of this mode of sedation.
Assuntos
Cuidados Críticos/métodos , Flumazenil/farmacologia , Midazolam/administração & dosagem , Adulto , Idoso , Hemodinâmica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Midazolam/antagonistas & inibidores , Midazolam/farmacologia , Pessoa de Meia-Idade , Respiração/efeitos dos fármacosRESUMO
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic disorder of the peripheral nervous system with sensory and motor involvement, and insidious onset over a period of months. In children and adults, both proximal and distal muscles are affected. Muscle stretch reflexes are absent or depressed. Laboratory findings include elevated cerebrospinal fluid protein with no increase of mononuclear cells. Electrophysiological and pathological studies show evidence of demyelination. No control studies of the efficacy of immunomodulating therapy in childhood CIDP are available. However, several studies have indicated clinical improvement after treatment with prednisolone, plasmapheresis and intravenous immunoglobulin, but disappointing results with other immunosuppressive agents. While some children have a monophasic course, with complete recovery, others have a protracted course, with either a slowly progressive or a relapsing-remitting course, resulting in prolonged morbidity and disability.
Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Adolescente , Biópsia , Criança , Pré-Escolar , Doença Crônica , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Lactente , Interferons/uso terapêutico , Condução Nervosa/fisiologia , Nervos Periféricos/fisiopatologia , Troca Plasmática/métodos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/etiologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Prognóstico , Esteroides/uso terapêutico , Nervo Sural/patologiaRESUMO
In a retrospective analysis of all our patients with seizure onset prior to age 16 years, 25 patients with primary generalized tonic (n = 10) or tonic-clonic (n = 15) seizures were identified. These patients constituted 5.7% of the total seizure patient population in our institute between the ages of 1 month and 16 years. The natural history of generalized tonic-clonic seizures is known to be benign; however, that of isolated primary generalized tonic seizures is not clear. Therefore, an attempt was made to characterize the patients suffering from primary generalized tonic seizures and determine their outcome. Analysis of our patient population shows that both seizure types are characterized by early onset of generalized seizures that appear in normally developed children with a normal electroencephalographic background. The children usually respond quickly to antiepileptic drugs. A long-term follow-up (mean period of 7.6 years) was possible in 84% of the patients, and showed that 95% of them were seizure free at the end of the follow-up period. There was no significant difference between the two groups in regard to age of onset, family history, and seizures at follow-up. In conclusion, the natural history of patients with generalized tonic seizures is similar to the benign course of those with generalized tonic-clonic seizures.
Assuntos
Epilepsia Generalizada/fisiopatologia , Convulsões/classificação , Convulsões/fisiopatologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Progressão da Doença , Epilepsia Tônico-Clônica/fisiopatologia , Seguimentos , Humanos , Lactente , Análise dos Mínimos Quadrados , Prognóstico , Estudos Retrospectivos , Convulsões/diagnósticoRESUMO
We present the family of two girls affected with alternating hemiplegia of childhood who were born to the same mother and different fathers. Previous reports suggested mitochondrial dysfunction as an etiologic mechanism for this disorder. Muscle biopsy, including a measurement of the respiratory chain enzymes, performed in one of the sisters showed no mitochondrial abnormalities. The mode of inheritance is not certain, but an autosomal-dominant gene is most likely.
Assuntos
Hemiplegia/diagnóstico , Hemiplegia/genética , Adolescente , Criança , Feminino , Humanos , Linhagem , PeriodicidadeRESUMO
Thirty-nine full-term babies, appropriate for gestational age, and otherwise healthy, were followed-up in our neurology clinic because of jitteriness, until complete resolution of symptoms and neurological findings. The babies were examined at 3 month intervals, and were classified according to the severity of their associated neurological findings, hypertonicity and increased tendon reflexes, into two groups: 'mild' (n = 24), and 'moderate-to-severe' (n = 15). The mean follow-up period was 13.5 months. In 81% of the study population, jitteriness and neurological findings disappeared before the age of 9 months. In only 11% did they persist beyond the age of 1 year. The mean time until disappearance of associated neurological findings was significantly shorter (5.5 months) in the mild group, compared to the moderate-to-severe group (9.5 months). Only one infant displayed motor delay and required physiotherapy.
Assuntos
Agitação Psicomotora , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Exame NeurológicoRESUMO
To establish the usefulness of electroencephalography (EEG) as a diagnostic tool in the evaluation of headaches in children, we retrospectively reviewed the records of all children referred to our outpatient neuropediatric clinic because of recurrent headaches. Of 312 children, 257 (82%) underwent EEG tracings: 143 of the children who had had EEG recordings were diagnosed as migraineurs. In 31 (12%) of the children, the EEG revealed epileptic activity. The highest incidence of epileptic EEG activity was found amongst the children with very brief headaches. In 22 (8.6%) of the children, diffuse or focal slowing was detected. The group with migraine headache had a significantly higher incidence of slowing than the group with other types of headaches. There was no correlation between focal EEG abnormalities and brain radioimaging studies or clinical course. We conclude that despite the high incidence of epileptic abnormalities, the contribution of EEG to diagnosis and treatment in children with chronic headache is minimal, and should not be routinely prescribed in these children.
Assuntos
Eletroencefalografia , Cefaleia/diagnóstico , Adolescente , Criança , Pré-Escolar , Doença Crônica , Feminino , Cefaleia/fisiopatologia , Humanos , Hiperventilação/fisiopatologia , Masculino , Estimulação Luminosa , Recidiva , Estudos RetrospectivosRESUMO
Three hundred and twelve children referred to an outpatient pediatric neurology clinic, with headache that lasted more than 3 months, were retrospectively reviewed. On average, the age of pain onset was 8.4 years. Migraine was diagnosed in 54% of these children and tension-type headache was found in 22% of those with chronic headache. Most children (85%) had common migraine, while classic and complicated migraine was found in only 8.8% and 5.3%, respectively. Brief headaches, lasting from seconds to a few minutes, were found in 5.1% of the children evaluated. In this subgroup, a high rate of epileptic EEG activity was found. Out of 110 children who had undergone computerized tomography, only one was pathological (posterior arachnoid cyst). Our results indicate that chronic and recurrent headache without accompanying neurological symptoms are usually benign and therefore in most cases neuroimaging is not indicated.
Assuntos
Cefaleia/diagnóstico , Adolescente , Distribuição por Idade , Fatores Etários , Cistos Aracnóideos/complicações , Cistos Aracnóideos/diagnóstico por imagem , Criança , Pré-Escolar , Doença Crônica , Diagnóstico Diferencial , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Feminino , Cefaleia/epidemiologia , Humanos , Masculino , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Tomografia Computadorizada por Raios XRESUMO
Whether seizures are the direct cause of cognitive deterioration in epileptic children is undetermined. This retrospective study aimed to delineate a subgroup of pediatric patients with cognitive deterioration and refractory seizures in the absence of recognized causes for mental retardation. Of the 80 children identified as having mental retardation and refractory seizure disorder, seven (8.7%) had normal cognitive development until at least 1 year of age. Their metabolic status was normal. Five of them suffered repeated frequent partial seizures with onset in the first year of life and two had repeated episodes of status epilepticus. All seven had similar characteristics of early onset partial seizures, six of them had partial seizures secondarily generalized and one had complex partial seizures. The time of peak cognitive deterioration correlated with increases in seizure frequency during that period. Evaluation revealed a well-defined epileptic focus in the absence of neuroimaging abnormality except for hippocampal atrophy in the two children with complex partial seizures and a small vascular malformation in one child. Uncontrolled partial seizures in the first months of life may result in cognitive deterioration.
Assuntos
Epilepsias Parciais/complicações , Epilepsias Parciais/fisiopatologia , Deficiência Intelectual/etiologia , Deficiência Intelectual/fisiopatologia , Adolescente , Fatores Etários , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Epilepsias Parciais/patologia , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/patologia , Estudos RetrospectivosRESUMO
Perifascicular atrophy of muscle fibers is generally considered to be a specific feature of autoimmune myopathies, dermatomyositis in particular. We describe a neonate presenting with hypotonia and weakness. A biopsy revealed atrophic and regenerating muscle fibers in a perifascicular distribution, and abnormal alkaline phosphatase activity in neighboring perimysial connective tissue. The weakness was nonprogressive and improved on follow-up even though no long-term treatment was administered. We conclude that the presence of perifascicular myopathic changes and muscle fiber atrophy in infants presenting with hypotonia and weakness is neither diagnostic of progressive dermatomyositis, nor a necessary indication for immunosuppressive therapy.