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2.
Brain Dev ; 43(1): 140-143, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32855001

RESUMEN

INTRODUCTION: Metachromatic leukodystrophy (MLD) refers to leukodystrophy caused by the accumulation of sulfatide from arylsulfatase A (ARSA) gene mutations. Sulfatide also accumulates in various organs, including the peripheral nerves, kidney, and gallbladder. Proliferative changes in the gallbladder have been reported in several patients, while gallbladder cancer is reported in only two adult MLD cases. We report what is likely the first pediatric case of MLD with gallbladder cancer. CASE REPORT: The patient was a 5-year-old girl diagnosed with MLD using head magnetic resonance imaging and detecting a homozygous mutation of c.302G>A (p.Gly101Asp) in ARSA. Abdominal bloating was observed at the age of 4 years; CT revealed a giant tumor in the gallbladder and massive ascites. Cholecystectomy was performed and pathological examination revealed adenocarcinoma. Measurement of serum sulfatide revealed increased levels compared to the average healthy range. DISCUSSION: Rapidly increased ascites and large polyps which are reported as risk factors for cancer were characteristic in our MLD case. When such lesions are detected, they should be removed immediately because of the possibility of cancer, even in a pediatric patient.

3.
Hum Gene Ther ; 2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33256498

RESUMEN

Niemann-Pick disease type C1 (NPC1) is a fatal congenital neurodegenerative disorder caused by mutations in the NPC1 gene, which is involved in cholesterol transport in lysosomes. Broad clinical manifestations of NPC1 include liver failure, pulmonary disorder, neurological deficits, and psychiatric symptoms. The main cause of death in NPC1 patients involves central nervous system (CNS) dysfunction; there is no essential treatment. We generated a tyrosine-mutant adeno-associated virus (AAV) 9/3 vector that expresses human NPC1 under a CMV promotor (AAV-CMV-hNPC1) and injected it into the left lateral ventricle (5 µl) and cisterna magna (10 µl) of Npc1 homo-knockout (Npc1-/-) mice. Each mouse received total 1.35×1011 vector genome on day 4 or 5 of life. AAV-treated Npc1-/- mice (n=11) had an average survival of >28 weeks, while all saline-treated Npc1-/- mice (n=11) and untreated Npc1-/- mice (n=6) died within 16 weeks. Saline-treated and untreated Npc1-/- mice lost body weight from seven weeks until death. However, the average body weight of AAV-treated Npc1-/- mice increased until 15 weeks. AAV-treated Npc1-/- mice also showed a significant improvement in Rotarod test performance. A pathological analysis at 11 weeks showed that cerebellar Purkinje cells were preserved in AAV-treated Npc1-/- mice. In contrast, untreated Npc1-/- mice showed an almost total loss of cerebellar Purkinje cells. Combined injection into both the lateral ventricle and cisterna magna achieved broader delivery of the vector to the CNS, leading to better outcomes than noted in previous reports with injection into the lateral ventricles or veins alone. In AAV-treated Npc1-/- mice, vector genome DNA was detected widely in the CNS and liver. Human NPC1 RNA was detected in the brain, liver, lung, and heart. Accumulated unesterified cholesterol in liver was reduced in the AAV-treated Npc1-/- mice. Our results suggest the feasibility of gene therapy for patients with NPC1.

4.
Am J Med Genet A ; 2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33251766

RESUMEN

Several patients with beta-propeller protein-associated neurodegeneration (BPAN)/static encephalopathy with neurodegeneration in adulthood have been reported to present Rett syndrome (RTT)-like features. This report presents an individual with BPAN showing clinical features of RTT. Psychomotor delay and epilepsy onset were noted at 1 year, and regression began at 4 years. Screening of the methyl-CpG binding protein 2 (MECP2) did not show variants. At 22 years, basal ganglia iron deposits were found on magnetic resonance imaging (MRI), and the WD-domain repeat 45 gene (WDR45) variant was identified. Review of the literature showed that BPAN with RTT-like features is associated with more epileptic seizures and less deceleration of head growth, breathing irregularities, and cold extremities than classic RTT with MECP2 variants. These clinical presentations may provide clues for differentiating between these two disorders. However, both WDR45 and MECP2 should be screened in patients presenting a clinical picture of RTT without specific MRI findings of BPAN.

6.
Clin Neurophysiol ; 131(9): 2100-2104, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32682237

RESUMEN

OBJECTIVE: The early diagnosis of beta-propeller protein-associated neurodegeneration (BPAN) before distinct brain magnetic resonance imaging (MRI) findings of iron deposition occur remains challenging. This study examined whether children with BPAN have characteristic high-amplitude (>50 µV) fast activity (HAFA) on electroencephalography (EEG). METHODS: We conducted a retrospective analysis of EEG performed during childhood in five patients with BPAN. We also examined 143 EEGs from 59 patients with different etiologies, including epilepsy (n = 33), acute encephalopathy (n = 6), neurodevelopmental disorders (n = 5), non-epileptic events (n = 4), and others (n = 11). Trained electroencephalographers reviewed all of the EEGs. When excessive fast activity was observed, the amplitude, frequency, and locality were assessed. RESULTS: All five patients with BPAN underwent initial EEGs at 12-21 months old, and diffuse continuous HAFA (range 20-50 Hz) was observed on both awake and sleep EEGs. In the awake records, there was no clear posterior dominant rhythm in 4 of the 5 patients. Although 28% of the 143 EEGs had continuous excessive fast activity, mainly in the sleep records, only two (1.4%) exhibited HAFA when asleep, and their awake EEGs had clear posterior dominant rhythm. CONCLUSIONS: The EEGs of children with BPAN showed diffuse HAFA continuously when both awake and asleep, which is uncommon in children with other etiologies. SIGNIFICANCE: This study provides an important clue for the early diagnosis of BPAN.

7.
BMC Pediatr ; 20(1): 342, 2020 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-32660452

RESUMEN

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by sleep apnea. Anoxia often occurs soon after birth, and it is important to prevent anoxia-mediated central nervous system complications; however, data on the relationship between respiratory management and the prognosis for intellectual development of patients with CCHS is not well yet investigate. METHODS: We performed a retrospective chart review cohort study of patients with CCHS in Japan. We investigated the risk and prognostic factors for developmental outcomes and examined the disease in terms of its symptoms, diagnosis, complications, and treatment. RESULTS: Of the 123 patients with CCHS included in the survey, 88 patients were 6 years old and older. They were divided into two group based on their intelligence quotient. Those treated using positive-pressure ventilation via tracheostomy in the first three months of life had a better developmental prognosis than those managed via tracheostomy after three months of age and those treated by ventilation using mask (OR = 3.80; 95% CI: 1.00-14.37, OR = 4.65; 95% CI: 1.11-19.37). There was no significant difference in physical development (P = 0.64). CONCLUSIONS: The best respiratory treatment for patients with CCHS is ventilation via tracheostomy, initiated ideally before the age of three months.

8.
Epileptic Disord ; 22(2): 214-218, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32301722

RESUMEN

Ring chromosome 20 syndrome is an epileptic and neurodevelopmental encephalopathy that occurs in children, characterised by a triad of refractory frontal lobe seizures, recurrent non-convulsive status epilepticus and frontal lobe-dominant paroxysmal discharges. However, details of other clinical features associated with ring chromosome 20 syndrome remain unknown. Here, we report two patients with ring chromosome 20 syndrome who had praxis-induced reflex seizures. Case 1 was an 11-year-old girl who presented with seizures triggered by specific activities such as mental and written calculations, writing, decision-making, recall, sudden changes in routine or ambient temperature and bathing. During calculations, left frontal lobe-dominant, 3-Hz slow-wave bursts were observed on EEG. Lacosamide effectively suppressed her tonic seizures. Case 2 was a six-year-old boy who presented with seizures triggered by specific activities such as calculations, recall and bathing. During calculations, frontal lobe-dominant, 3-Hz spike and slow-wave bursts were observed on EEG. Although his epilepsy was refractory, gabapentin reduced the frequency of focal seizures. In both cases, the hyperexcitability in the frontal lobe may have spread to the motor cortex and precipitated praxis-induced seizures. Therefore, in addition to the known characteristic triad, praxis-induced reflex seizures may also be a feature of ring chromosome 20 syndrome.

9.
Brain Dev ; 42(7): 529-533, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32336483

RESUMEN

BACKGROUND: A report presenting five heterozygous de novo variants in VAMP2 in unrelated individuals with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features was first published in April 4, 2019. CASE REPORT: We report the case of a male child with VAMP2 variant who was delivered at 38 weeks and 4 days without neonatal asphyxia. At 4 months of age he showed hypotonia and no visual pursuit and fixation. He presented with infantile spasms at 6 months, and electroencephalography (EEG) showed hypsarrhythmia. His infantile spasms completely disappeared by adrenocorticotropic hormone therapy, but his EEG findings continued to show high voltage slow-waves with multi-focal spikes. At 2 years of age he was non-verbal, had an absence of purposeful hand movements, and no visual fixation. He had somnolence tendency in the daytime. Biochemical and extensive genetic examinations were unrevealed. Magnetic resonance imaging showed slight brain atrophy. At 2 years and 7 months of age, he suffered from myoclonic seizures of the eyelid and tongue, which propagated to unilateral fingers, and sometimes to the bilateral legs. At 8 years of age hyperkinetic movement occurred. At age 13, whole-exome sequence identified a heterozygous missense variant, NM_014232.2:c.199G>C,[p.(Ala67Pro)] in exon 3 of VAMP2 which was a de novo non-synonymous variant. CONCLUSION: This is the first case report of VAMP2 variant in Japan. Hypotonia at early infancy, poor visual fixation, and absence of purposeful hand movements may be indicative of the diagnosis for VAMP2 variant.

10.
Sci Rep ; 9(1): 16344, 2019 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-31704978

RESUMEN

Idiopathic restless legs syndrome (RLS) has a genetic basis wherein BTBD9 is associated with a higher risk of RLS. Hemodialysis patients also exhibit higher rates of RLS compared with the healthy population. However, little is known about the relationship of BTBD9 and end-stage renal disease to RLS pathophysiology. Here we evaluated sleep and leg muscle activity of Btbd9 mutant (MT) mice after administration of serum from patients with either idiopathic or RLS due to end-stage renal disease (renal RLS) and investigated the efficacy of treatment with the dopamine agonist rotigotine. At baseline, the amount of rapid eye movement (REM) sleep was decreased and leg muscle activity during non-REM (NREM) sleep was increased in MT mice compared to wild-type (WT) mice. Wake-promoting effects of rotigotine were attenuated by injection of serum from RLS patients in both WT and MT mice. Leg muscle activity during NREM sleep was increased only in MT mice injected with serum from RLS patients of ideiopatic and renal RLS. Subsequent treatment with rotigotine ameliorated this altered leg muscle activity. Together these results support previous reports showing a relationship between the Btbd9/dopamine system and RLS, and elucidate in part the pathophysiology of RLS.


Asunto(s)
Músculos/fisiología , Fenómenos Fisiológicos Musculoesqueléticos , Proteínas del Tejido Nervioso/fisiología , Síndrome de las Piernas Inquietas/sangre , Suero/química , Sueño REM/fisiología , Tetrahidronaftalenos/farmacología , Tiofenos/farmacología , Animales , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Agonistas de Dopamina/farmacología , Humanos , Fallo Renal Crónico/terapia , Masculino , Ratones , Ratones Noqueados , Músculos/efectos de los fármacos , Diálisis Renal/efectos adversos , Síndrome de las Piernas Inquietas/etiología , Síndrome de las Piernas Inquietas/patología , Sueño REM/efectos de los fármacos
11.
Heliyon ; 5(8): e02229, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31497663

RESUMEN

In the magnetic field analysis of magnetic devices using a ferrite core, such as a pulse transformer, the frequency-domain analysis is often carried out using the measured complex permeability under different frequency range. However, the nonlinear magnetic characteristics cannot be considered in the frequency-domain analysis because of the harmonics caused by it cannot be represented. The nonlinear magnetic characteristics can be considered in the time-domain analysis, but suitable constant conductivity and permittivity taking account of the microstructure of ferrite core, which can represent the measured complex permeability under different frequencies, needs to be investigated for the time-domain analysis. In this paper, the effective permeability of a toroidal ferrite core is tried to be demonstrated by using the linear ac steady state magnetic field analysis taking account eddy currents and displacement currents. It is shown that the measured permeability can be realized roughly by using the modified constant conductivity and permittivity. The nonlinear time-domain magnetic field analysis can be carried out using the modified constant conductivity and permittivity obtained from this paper.

12.
Brain Dev ; 41(8): 726-730, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31029456

RESUMEN

INTRODUCTION: Neuronal ceroid lipofuscinoses (NCLs; CLN) are mainly autosomal recessive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigments in neuronal and other cells. Symptoms include visual disabilities, motor decline, and epilepsy. Causative genes are CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8, CLN10, CLN11, CLN12, CLN13, and CLN14. We present the fourth Japanese case with a CLN6 mutation. CASE PRESENTATION: At 3 years of age, our patient became clumsy and fell down easily. He developed focal seizures with impaired consciousness and was started on carbamazepine. He showed ataxic walking and dysarthria with increased deep tendon reflexes. Interictal electroencephalogram revealed slow waves in the left temporal and occipital areas. Brain magnetic resonance imaging showed cerebellar atrophy and ventriculomegaly. In optical coherence tomography (OCT), the inner layer of the retina was thick and highly reflective. Exome sequencing revealed a known homozygous mutation, C.794_976del, p. (Ser265del) in CLN6. DISCUSSION: A total of 130 cases of NCL with CLN6 mutations have been reported globally, of which only four were from Japan including the current patient. The deletion of serine at position 265 has been reported in six cases. Ser265 is located in a region of short repeated sequences that is susceptible to mutation. Clinical trials of gene therapy using adeno-associated virus serotype 9 have started for NCL6, making early diagnosis crucial. OCT examination might be helpful in achieving a diagnosis.


Asunto(s)
Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Lipofuscinosis Ceroideas Neuronales/genética , Preescolar , Progresión de la Enfermedad , Epilepsia/genética , Homocigoto , Humanos , Japón , Masculino , Limitación de la Movilidad , Mutación , Lipofuscinosis Ceroideas Neuronales/metabolismo , Convulsiones/genética , Caminata/fisiología
13.
Brain Dev ; 41(5): 465-469, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30739820

RESUMEN

Mutations in the mitochondrial tRNAMet gene have been reported in only five patients to date, all of whom presented with muscle weakness and exercise intolerance as signs of myopathy. We herein report the case of a 12-year-old girl with focal epilepsy since the age of eight years. At age 11, the patient developed sudden visual disturbances and headaches accompanied by recurrent, stroke-like episodes with lactic acidosis (pH 7.279, lactic acid 11.6 mmol/L). The patient frequently developed a delirious state, exhibited regression of intellectual ability. Brain magnetic resonance imaging revealed high-intensity signals on T2-weighted images of the left occipital lobe. Mitochondrial gene analysis revealed a heteroplasmic m.4450G > A mutation in the mitochondrial tRNAMet. The heteroplasmic rate of the m.4450G > A mutation in blood, skin, urinary sediment, hair, saliva, and nail samples were 20, 38, 59, 41, 27, and 35%, respectively. The patient's fibroblast showed an approximately 53% reduction in the oxygen consumption rate, compared to a control, and decreased complex I and IV activities. Stroke-like episodes, lactic acidosis, encephalopathy with brain magnetic resonance imaging findings, and declined mitochondrial function were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. To our knowledge, the findings associated with this first patient with MELAS syndrome harboring the m.4450G > A mutation in mitochondrial tRNAMet expand the phenotypic spectrum of tRNAMet gene.


Asunto(s)
Síndrome MELAS/diagnóstico , Síndrome MELAS/genética , Síndrome MELAS/fisiopatología , ARN Mitocondrial/genética , ARN de Transferencia de Metionina/genética , Niño , Femenino , Humanos
15.
Brain Dev ; 40(3): 242-246, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28958731

RESUMEN

INTRODUCTION: The relevant literature includes several case reports on cerebral infarction in children with HHV-6 infection; however, there is no report of brain stem infarction. CASE: An 11-month-old girl was hospitalized because of fever. She was unable to stand up and meet her mother's gaze. Magnetic resonance imaging (MRI) indicated a right pons and mid-brain lesion; a diagnosis of brainstem infarction was made. After her fever subsided, a rash developed on her trunk and limbs; blood examination results indicated a primary HHV-6 infection. She was treated with aspirin, edaravone, and mannitol to prevent further complications. At the age of 18months, the auditory brainstem response (ABR) was unremarkable and she is developing well. DISCUSSION AND CONCLUSION: A limited number of studies have reported HHV-6 infection-associated infarction, and no cases of brainstem infarction have been reported. One possible cause of cerebral infarction is antiphospholipid antibody syndrome (APS) triggered by the infection. HHV-6 may also directly infect vascular endothelial cells and cause angiopathy. However, the real mechanism of infarction remains unclear. Our patient had a favorable prognosis despite brainstem infarction.


Asunto(s)
Infartos del Tronco Encefálico/etiología , Herpesvirus Humano 6/patogenicidad , Infecciones por Roseolovirus/complicaciones , Antiinflamatorios/uso terapéutico , Infartos del Tronco Encefálico/diagnóstico por imagen , Infartos del Tronco Encefálico/tratamiento farmacológico , Infartos del Tronco Encefálico/virología , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Infecciones por Roseolovirus/diagnóstico por imagen , Infecciones por Roseolovirus/tratamiento farmacológico
16.
Environ Sci Pollut Res Int ; 25(17): 16300-16308, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29204936

RESUMEN

It is necessary for companies supplying reclaimed oil to analyze polychlorinated biphenyls (PCBs), because there is a possibility of the presence of contaminants due to trace-level PCBs in the reclaimed oil. However, common analysis methods of PCBs are time-consuming and complicated. Fast-GC triple stage quadrupole mass spectrometer with the 13-component quantitation method is an official method for analyzing PCBs in insulating oil in Japan. This method is extremely fast and simplified. The purpose of this study involves an investigation of the aforementioned fast and simple method for potential use in the analysis of reclaimed oil. Furthermore, it was attempted to combine the method with sample preparation involving only hexane dilution. The effect of sample dilutions corresponding to 100, 300, and 500 times was evaluated for reducing the matrix effect. The matrix effect was suppressed at a dilution ratio equal to or exceeding 300 times. Calibration curves of four points, namely 0.01, 0.05, 0.1, and 0.5 ng/mL, (ignored origin) by using an internal standard method were prepared for the 13 components. The square of regression coefficient (R2) values of all calibration curves exceeded 0.997. This method was adopted for the analysis of reclaimed oil containing 0.5 µg/mL PCBs, which corresponds to the judgment criteria, and accurate quantitation (accuracy value, 94.0-102%) and good repeatability (%RSD, 3.6%) were obtained. Furthermore, the required sensitivity was maintained even when 800 samples were analyzed without a cleaning ion source and an exchanging analysis column.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas/métodos , Bifenilos Policlorados/análisis , Técnicas de Dilución del Indicador , Bifenilos Policlorados/química
17.
Pediatr Int ; 59(8): 951-954, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28804976

RESUMEN

Herein we report the case of a 6-year-old girl with autism spectrum disorder (ASD) and weakness in the distal portion of the right upper limb. Although difficult to perform, nerve conduction studies indicated demyelinating neuropathy. Magnetic resonance imaging (MRI) showed swelling a nd high-intensity signals in the right brachial plexus and cervical spinal roots. The symptoms recovered after a single course of i.v. immunoglobulin. Electrophysiological indices and MRI findings also improved after treatment. This case demonstrates the utility of neuroimaging in addition to electrophysiological assessments for the diagnosis of demyelinating neuropathy, particularly in young patients with ASD.


Asunto(s)
Trastorno del Espectro Autista/complicaciones , Enfermedades Desmielinizantes/diagnóstico por imagen , Imagen por Resonancia Magnética , Neuroimagen , Niño , Enfermedades Desmielinizantes/complicaciones , Femenino , Humanos
18.
Nat Genet ; 49(3): 457-464, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28092684

RESUMEN

Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg2+-dependent 3'-end RNases with substrate specificity that is mostly unknown. Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia. We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1, which encodes an unconventional deadenylase. toe1-morphant zebrafish displayed midbrain and hindbrain degeneration, modeling PCH-like structural defects in vivo. Surprisingly, we found that TOE1 associated with small nuclear RNAs (snRNAs) incompletely processed spliceosomal. These pre-snRNAs contained 3' genome-encoded tails often followed by post-transcriptionally added adenosines. Human cells with reduced levels of TOE1 accumulated 3'-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3'-end maturation of snRNAs. Our findings identify the cause of a neurodegenerative syndrome linked to snRNA maturation and uncover a key factor involved in the processing of snRNA 3' ends.


Asunto(s)
Enfermedades Cerebelosas/genética , Exonucleasas/genética , Mutación/genética , Proteínas Nucleares/genética , ARN Nuclear Pequeño/genética , Alelos , Animales , Femenino , Humanos , Masculino , Ratones , Enfermedades Neurodegenerativas/genética , ARN Mensajero/genética , Empalmosomas/genética , Pez Cebra
19.
Brain Dev ; 39(3): 231-235, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27745925

RESUMEN

INTRODUCTION: Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID). METHODS: We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment ⩾2years, (2) younger than 20years old, and (3) received oral levetiracetam treatment for ⩾6months. We assessed the relationships of these outcomes with MRI findings and ID status. RESULTS: Eighteen (37%) patients achieved a ⩾50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patients who achieved a ⩾50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively. CONCLUSIONS: Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Piracetam/análogos & derivados , Administración Oral , Adolescente , Anticonvulsivantes/administración & dosificación , Niño , Preescolar , Quimioterapia Combinada/métodos , Tolerancia a Medicamentos , Femenino , Humanos , Levetiracetam , Masculino , Piracetam/administración & dosificación , Piracetam/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
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